AddCisplatinToGem+NabPaclitaxel2017

Cisplatin Added to Gemcitabine / Nab-Paclitaxel Everyone, In my post immediately above I failed to say that one does not have to be a clinical trial participant in order to receive the 3-drug Cisplatin/Gemcitabine/Nab-Paclitaxel regimen, since the agents are readily available off-trial Assuming that the disease has not progressed on a Gemcitabine regimen, all the patient needs is a willing oncologist skilled in managing related adverse events – and the regimen protocol, which is described in the trial record and at the end of this doc file: https://clinicaltrials.gov/show/NCT01893801 http://jaxelection.altervista.org/pancreatic/AddCisplatinToGem+NabPaclitaxel2017.doc This may not be an approved regimen, so insurance may not cover it, although a clever provider may be able to manage the coverage The regimen appears to aid those affected by BRCA mutations (which is many pancreatic cancer victims) PhilipJax For “Advanced” & Metastatic Patients Everyone, Two items: ASCO has released its guidelines for treating metastatic disease It is not so significant as the NCCN guidelines So, study both, which are available here: http://jaxelection.altervista.org/pancreatic/ASCO_MetastaticGuidelines2016.017368.pdf http://jaxelection.altervista.org/pancreatic/NCCN1.2017PancreaticUnlocked.pdf Published today: the results of a small (so less reliable) study of 24 “advanced” patients show good performance when cisplatin is added to standard gemcitabine/nab-paclitaxel 17 of 24 patients (71%) experienced tumor-size reductions of at least 30% Two had complete responses, which is a very desirable and rare event And, median overall survival was 16.5 months See http://jaxelection.altervista.org/pancreatic/AddCisplatinToGem+NabPaclitaxel2017.doc There are several ongoing clinical trials which utilize the 3-drugs See >> Stage 4, non-randomized: https://clinicaltrials.gov/show/NCT02754726 >> Stage or 4, non-randomized: https://clinicaltrials.gov/show/NCT02227940 >> “Advanced” and Stage 4, non-randomized: https://clinicaltrials.gov/show/NCT02495896 >> Resectable & potentially-resectable: https://clinicaltrials.gov/show/NCT02550327 >> Resectable & potentially-resectable: https://clinicaltrials.gov/show/NCT01726582 Usually, in non-randomized studies all patients get the experimental agents Also, be cautions about trials which include immuno agents On occasion, some have accelerated the disease greatly See http://jaxelection.altervista.org/pancreatic/HyperprogressOnImmunotherapy_Nivolumab2017 doc In the last trial NCT01726582 the principal investigator is Douglas B Evans, M.D., FACS, who may be the same highly-skilled surgical oncologist who once served at MD Anderson PhilipJax Response Rates Improved With Platinum Added to NabPaclitaxel/Gemcitabine in Advanced Pancreatic Cancer Wayne Kuznar | Thursday, Feb 16, 2017 | http://www.onclive.com/web-exclusives/responserates-improved-with-platinum-added-to-nabpaclitaxelgemcitabine-in-advanced-pancreaticcancer Clinical trial information: NCT01893801 The addition of a platinum agent to standard gemcitabine and nab-paclitaxel was found to be associated with impressive response and overall survival (OS) rates in patients with stage IV pancreatic cancer, according to findings of a small pilot trial presented at the 2017 Gastrointestinal Cancers Symposium.1 With 11 of 25 patients [44%] in the study still alive, the median OS is 16.5 months, said Gayle Jameson, MSN, ACNP-BC, AOCN, when presenting the findings at the meeting “We have not seen that in stage IV pancreatic cancer to date It’s a very small study though,” she said “The median survival will continue [to increase] because the data are not mature and we still have 11 patients alive.” The genomes of patients with metastatic pancreatic cancer contain myriad intrachromosomal aberrations, indicating a high prevalence of DNA repair deficiencies In the phase II Stand Up Cancer trial, every patient with pancreatic ductal adenocarcinoma had multiple interstitial copy number aberrations,2 noted Jameson, nurse practitioner and associate investigator of Clinical Trials, HonorHealth Research Institute, Scottsdale Healthcare Research Institute “These types of tumors are very sensitive to platinums, which are DNA-damaging agents,” she said Twenty-five patients with stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, Karnofsky performance status (KPS) ≥70%; life expectancy ≥12 weeks, and measurable disease were enrolled at US sites between December 2013 and July 2016 Nab-paclitaxel was administered at 125 mg/m2 undiluted, gemcitabine at 1000 mg/m2, each infused over 30 minutes on days and of a 21-day cycle In addition, patients received either 25 mg/m2 of cisplatin infused over 60 minutes, escalated to 50 mg/m2, after the nabpaclitaxel infusion Median age of the patients was 65 years, all had KPS ≥80%, and 79% had an elevated CA19-9 at baseline Primary tumor location was the head of the pancreas in 24%, body in 32%, and tail in 24% Twenty percent had their tumor resected The maximum tolerated and phase II dose of cisplatin was 25 mg/m “It’s a very low dose of cisplatin, but adding that we’ve seen a very impressive response rate,” she said The overall response rate (ORR) by RECIST v1.1 criteria was 71%, with complete responses (8.3%) and 15 partial responses (62.5%) The 71% ORR is “exceptional in stage IV pancreas disease,” Jameson indicated Most patients who had an abnormal level of CA199 at baseline had values decline by 50% to 100% within 90 days Eighteen of the 25 patients [72%] had a ≥30% reduction in tumor size from baseline, and of the 25 had a resolution of measurable tumor by RECIST criteria The median survival to date of 16.5 months “has not been seen in stage IV pancreatic cancer,” she said Some 64% of patients were alive at 12 months, 20% were alive at 24 months, 4% were still alive at 36 months, with 11 of the 25 patients still alive at last follow-up The most common drug-related grade ≥3 adverse events were thrombocytopenia (76% total; grade 3, 36%; grade 4, 40%) with no serious bleeding events, anemia in 32% (all grade 3), neutropenia in 24% (grade 3, 20%; grade 4, 4%), infection in 20% (grade 3, 16%; grade 4, 4%), and grade diarrhea in 16% “We’d like to expand the study but we also have a tissue analysis that’s upcoming,” said Jameson “As we look for genomic signatures of response, this is going to be key.” A study examining this triplet in the neoadjuvant setting is also planned References Jameson GS, Borazanci E, Babiker HM, et al A phase Ib/II pilot trial with nab-paclitaxel plus gemcitabine plus cisplatin in patients (pts) with stage IV pancreatic cancer Presented at: 2017 Gastrointestinal Cancers Symposium; January 19-21, 2017; San Francisco, CA Abstract 341 Barrett MT, Lenkiewicz, Evers L, et al Abstract 3697: phase II study of therapy selected by molecular profiling in patients with previously treated metastatic pancreatic cancer – SU2C-001 Cancer Res 2012;72(8 suppl):abstr 3697 doi:10.1158/1538-7445.AM20123697 A phase Ib/II pilot trial with nabpaclitaxel plus gemcitabine plus cisplatin in patients (pts) with stage IV pancreatic cancer Subcategory: Multidisciplinary Treatment Category: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract Meeting: 2017 Gastrointestinal Cancers Symposium Session Type and Session Title: Poster Session B: Cancers of the Pancreas, Small Bowel and Hepatobiliary Tract Abstract Number: 341 Poster Board Number: Poster Session B Board #F11 Citation: J Clin Oncol 35, 2017 (suppl 4S; abstract 341) Author(s): Gayle S Jameson, Erkut Hasan Borazanci, Hani M Babiker, Elizabeth Poplin, Anna A Niewiarowska, Michael S Gordon, Michael T Barrett, Karen Ansaldo, Leticia Lebron, Amy C Stoll, Adam Rosenthal, Lynn R Shemanski, Ronald Lee Korn, Ramesh K Ramanathan, Daniel D Von Hoff; HonorHealth/TGen, Scottsdale, AZ; University of Arizona Cancer Center, Tucson, AZ; Cancer Institute of New Jersey, New Brunswick, NJ; Vita Medical Associates, Fountain Hill, PA; Pinnacle Oncology Hematology/Honor Health Research Institute, Scottsdale, AZ; Mayo Clinic Cancer Center, Scottsdale, AZ; HonorHealth, Scottsdale, AZ; Cancer Research And Biostatistics, Seattle, WA; Cancer Research and Biostatistics, Seattle, WA; Scottsdale Medical Imaging, Ltd., Scottsdale, AZ; Translational Genomics Research Institute (TGen) and HonorHealth, Phoenix and Scottsdale, AZ Abstract: Background: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations indicating DNA repair abnormalities associated with sensitivity to DNA damaging agents such as the platinums Cisplatin was added to a nab-paclitaxel + gemcitabine regimen, which has been determined to improve survival over gemcitabine alone (NEJM 2013; 369:1691-1703) The objectives are to determine the efficacy and safety of nabpaclitaxel and gemcitabine plus cisplatin in patients with Stage IV pancreatic cancer Methods: Eligibility criteria included Stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease Doses are nab-paclitaxel 125 mg/m2 undiluted, gemcitabine 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes on days and of a 21 day cycle, along with different dose levels of cisplatin (25, 37.5 or 50 mg/m 2) in 500 ml of NS infused over 60 minutes, after the nab-paclitaxel infusion Pre and post cisplatin hydration was given The maximum tolerated dose and phase II dose of cisplatin is 25 mg/m Results: 25 pts were treated; 24 were evaluable (baseline and ≥ follow up CT scan) The most common drug related grade (gr) - adverse events (AEs), n = 25, were thrombocytopenia 76% (gr = 36%, gr = 40%) with no serious bleeding events, anemia 32% (gr = 32%, gr = 0%), neutropenia 24% (gr = 20%, gr = 4%), infection 20% (gr = 16%, gr = 4%), and diarrhea 16% (gr = 16%, gr = 0%) Peripheral neuropathy ≥ gr was seen in only pt (gr = 4%) Grade AEs were infection (1), cardiac arrest (1), and stroke (1) Median time on therapy was 5.5 months, range (1 – 9.5) By RECIST 1.1 criteria, pts had complete response (8.3%), 15 partial response (62.5%), stable disease (16.7%), and progressive disease (12.5%) Median overall survival to date as of 11/10/16 is 16.5 months Conclusions: Although a small study, the high response rate and landmark evolving median survival are very encouraging This regimen is being expanded in patients with stage IV pancreatic cancer, neoadjuvant and adjuvant settings Clinical trial information: NCT01893801 Unfolding: Gemcitabine + Abraxane + Cisplatin for Stage Pancreatic Cancer By Pancreatica | Published February 15, 2017 http://pancreatica.org/unfolding-gemcitabineabraxane-cisplatin-stage-4-pancreatic-cancer/ Since the mid-1990s, teams affiliated with Dr Daniel Von Hoff have ushered in two of the three key advances in the first-line treatment of advanced pancreatic cancer (ductal adenocarcinoma of the pancreas) This includes seminal work from a research institute affiliated with the University of Texas at San Antonio on the development of gemcitabine for the treatment of pancreatic cancer, AND per published article in 2013 as acting lead of an international consortium presenting the MPACT study results that represented a formal introduction to the advantages of gemcitabine plus Abraxane (nab-paclitaxel) in the treatment of metastatic pancreatic cancer The other key advance was the 2011 article in the New England Journal of Medicine by French researchers demonstrating the survival advantage of the 4-drug regimen known as FOLFIRINOX over gemcitabine alone in the therapy for advanced pancreatic cancer Now another treatment improvement from a new Von Hoff team that appears, at least thus far, to offer potential further increased survival advantage First in the April 2015 American Association for Cancer Research (AACR) annual meeting, and later at the January 2017 Gastrointestinal Cancers Symposium (American Society of Clinical Oncology – ASCO) Von Hoff’s team from HonorHealth Research Institute in Scottsdale, Arizona and other institutions, including fellow researchers Gayle S Jameson, Erkut Borazanci and other authors, have reported out the rolling results of an ongoing Phase Ib/II clinical trial that assess the addition of cisplatin to the original gemcitabine plus Abraxane regimen in the treatment of metastatic pancreatic cancer (clinical trial: NCT01893801) In the 2015 AACR meeting, the researchers published their work in a meeting abstract entitled, “High complete and partial response rate in a phase Ib pilot trial with cisplatin plus albumin-bound paclitaxel and gemcitabine in patients with advanced pancreatic cancer.” Under the rationale that pancreatic cancer not infrequently demonstrates abnormalities in DNA repair that may tend to respond to such entities as platinum salts, they added cisplatin to the gemcitabine plus Abraxane chemotherapy regimen for patients with stage IV pancreatic cancer Ten patients with advanced pancreatic cancer were enrolled with two showing a complete response, six showing a partial response, one offering stable disease, and one demonstrating progression of their pancreatic cancer Four patients had serious adverse side effects including sepsis/pneumonia, bacteremia, clostridium difficile colitis, and neutropenic fever/pneumonia Despite the sobering events profile, the clinical results were encouraging enough for the researchers to move forward to the stage II status of the clinical trial In the 2017 Gastrointestinal Cancers Symposium, the research team both published an abstract and presented their further results in a Poster Presentation, “A phase Ib/II pilot trial with nab-paclitaxel plus gemcitabine plus cisplatin in patients with stage IV pancreatic cancer.” The 25 patients in three U.S sites met inclusion criteria including being diagnosed with stage IV pancreatic cancer between December 2013 and July 2016 All of the patients were treated with the three-drug regimen 20% had their tumor resected 18 of the 25 patients had a greater than 30% reduction in the pancreatic cancer tumor size The median survival to date (at the time of presentation) was 16.5 months, with 20% alive at 24 months 40% of the patients experienced a grade adverse effect including primarily such conditions as thrombocytopenia, anemia, neutropenia, infection, or substantive diarrhea Dr Erkut Borazanci indicated that there appears to be, “something related to ‘BRCA-ness’ in pancreatic tumors,” referring to the positive response that patients with BRCA1 or BRCA2 genetic-mutation-related cancers tend to have to platinum drugs (and perhaps PARP inhibitors) Please note our Pancreatica Blog on this topic Here These preliminary survival outcome results with the cisplatin + gemcitabine + Abraxane regimen for advanced pancreatic cancer are remarkably encouraging, to say the least The adverse effects of this chemotherapy regimen though are rather profound, and would require serious management and care One interesting finding was the high number of patients who became available for surgery during the course of the treatment (the authors have indicated that a separate study of this outcome is anticipated) It is important to note that these are meeting results with a small number of patients, and the results are not yet published in a peer-reviewed journal It will be highly interesting to see if the outcomes of this treatment approach hold up in a Phase III trial, and as peer reviewed If so, the current Von Hoff team will have again succeeded in changing the landscape of the treatment for advanced pancreatic cancer References Proceedings: AACR 106th Annual Meeting; April 18-22, 2015; Philadelphia, PA; Cancer Res 2015;75(15 Suppl):Abstract LB-003 doi:10.1158/1538-7445 2017 Gastrointestinal Cancers Symposium, ASCO, San Francisco; J Clin Oncol 35, 2017 (suppl 4S; abstract 341); Poster Session B Board #F11 Dale O’Brien, MD Phase Ib/II Study Reports High Response Rates Seen With Addition of Cisplatin to Regimen for Advanced Pancreatic Cancer By Caroline Helwick | April 10, 2016 | http://www.ascopost.com/issues/april-10-2016/phaseibii-study-reports-high-response-rates-seen-with-addition-of-cisplatin-to-regimen-foradvanced-pancreatic-cancer/ An 80% response rate with traditional chemotherapy is basically unheard of [in advanced pancreatic cancer] But we know this is a very small sample, and we are very cautious — Gayle Jameson, MSN, ACNP-BC, AOCN The oncology research team at HonorHealth Research Institute in Scottsdale, Arizona, is spearheading a phase Ib/II trial that is demonstrating promising results with a novel regimen in patients with advanced pancreatic cancer “The patients we are treating have advanced adenocarcinoma of the pancreas, for which survival is typically very grim,” said principal investigator of the clinical trial Gayle Jameson, MSN, ACNP-BC, AOCN “We have added a third drug to the two-drug combination of albumin-bound paclitaxel/gemcitabine, which originated here at our center, and the responses we have seen in the first 10 patients are remarkable in several ways,” she revealed Albumin-bound paclitaxel, or paclitaxel protein-bound particles for injectable suspension (Abraxane), was formerly known as nab-paclitaxel Ms Jameson and co-investigator Erkut Borazanci, MD, MS, described their study in an interview with The ASCO Post Ms Jameson said they are excited to share positive results in this challenging malignancy “We want to instill hope, not only in patients but also in physicians, nurses, and oncology teams,” she said “Many patients come to us for a second opinion, after their oncologist has told them to get their affairs in order We now have multiple options for stage IV cancer It’s a new ballgame, and there are choices that patients can make to potentially improve the quantity and quality of their lives.” Study Details and Rationale Data available on the first 10 patients were reported at the 2015 American Association for Cancer Research Annual Meeting.1 Based on the encouraging responses observed, the phase II part of the study was expanded to enroll 25 patients, 20 of whom have been treated The trial is evaluating a regimen of albumin-bound paclitaxel/gemcitabine plus cisplatin The choice of cisplatin is based on the recent discovery that pancreatic cancers contain chromosomal aberrations indicative of DNA-repair deficiencies, which are often sensitive to DNA-damaging agents “Looking at the genome, we see changes that speak to the fact that there is something related to ‘BRCA-ness’ in pancreatic tumors The idea is that we can target these global aberrations with DNA-damaging agents, such as cisplatin,” Dr Borazanci explained This treatment requires a lot of attention In our center, we are very responsive to the needs of our patients A lot of supportive care is needed around this regimen [of cisplatin plus nab-paclitaxel/gemcitabine] — Erkut Borazanci, MD, MS To be eligible for the phase Ib/II study, patients must have stage IV pancreatic cancer and no prior chemotherapy for systemic disease, a Karnofsky performance status ≥ 70, a life expectancy ≥ 12 weeks, and measurable disease In phase Ib, patients received albumin-bound paclitaxel at 125 mg/m2 undiluted and gemcitabine at 1,000 mg/m2, each infused over 30 minutes on days and of a 21-day cycle They also received cisplatin at one of three doses—25, 37.5, or 50 mg/m2—after the albumin-bound paclitaxel infusion In phase II, all patients will receive cisplatin at 25 mg/m2, which was determined to be the maximum tolerated dose Preliminary Results Of the 10 patients treated in phase Ib, the response rate was 80%, including complete responses (20%), partial responses (60%), patient with stable disease (10%) and patient with progressive disease (10%) “An 80% response rate with traditional chemotherapy is basically unheard of,” Ms Jameson commented “But we know this is a very small sample, and we are very cautious We can’t make big claims based on 10 patients, but we are very encouraged.” These responses occurred early, by the first staging evaluation, in seven patients Responses were accompanied by exponential decreases in CA19-9 in the six patients with elevated CA19-9 at baseline Maximal percentage change from baseline was 40% to 100% for these six patients “We saw a very prompt drop in the CA-19 marker and a very rapid response by decreases in RECIST [Response Evaluation Criteria in Solid Tumors] measurements After three cycles, by weeks, we saw markers plummet and tumors shrink, and we also saw patients feeling better,” Ms Jameson noted Some responses have been durable, she added “One of our patients with a complete response after 12 cycles is alive years and months after starting this regimen and has no evidence of disease,” she reported The investigators have not yet reported results for the 20 patients treated in the expanded phase but indicated they “continue to be encouraged.” Impact of Cisplatin The ASCO Post asked the investigators to what degree cisplatin added to the benefit seen with standard regimens in this disease The phase III MPACT trial established nab-paclitaxel/gemcitabine as first-line treatment, with a 28% reduction in mortality (P < 001) over gemcitabine alone.2 The response rate, by independent review, was 23% with the doublet vs 7% with gemcitabine alone (P < 001) Similarly, with FOLFIRINOX (fluorouracil/leucovorin/irinotecan/oxaliplatin), the response rate in the pivotal French phase III trial was 31.6% in the FOLFIRINOX group vs 9.4% in the gemcitabine group (P < 001).3 Interestingly, the addition of cisplatin to gemcitabine has not been shown to improve survival in other previous studies “This goes back to the idea of building upon other successes We know that albumin-bound paclitaxel is synergistic with gemcitabine Based upon genomic research in pancreas cancer,4 we think that the addition of cisplatin may add even greater synergy,” Dr Borazanci said “I don’t want to compare this small population to those other trials, and there are certainly no head-to-head studies, but from what we’re seeing so far, the outcomes in our study are unique,” he said Ms Jameson added: “To see of 10 patients so well has been very exciting.” Tolerability “Patients are tolerating the regimen well, but we have a strong focus on supportive care,” said Ms Jameson The investigators expected to see more neuropathy and renal toxicity, but so far, the toxicities have not been more than anticipated “What we actually see is that, because of the rapid response, some patients feel better much more quickly Several patients who presented with significant pain were able to completely wean off of narcotics,” Ms Jameson reported Adverse events grade ≥ were observed in 60% and ≥ 4, in 30% of patients Serious adverse events occurred in four patients, including non-neutropenic sepsis/pneumonia, nonneutropenic bacteremia, neutropenic fever/pneumonia, and Clostridium difficile colitis Is Regimen Ready for the Clinic? Ms Jameson and Dr Borazanci are aware that oncologists may see these results and try this regimen on their own patients Those doing so should be aware, said Dr Borazanci “This treatment requires a lot of attention In our center, we are very responsive to the needs of our patients A lot of supportive care is needed around this regimen,” he noted The clinicians’ biggest concerns have been the prevention of dehydration, neuropathy, and fatigue They use intravenous fluids liberally “It’s not been completely smooth sailing,” he acknowledged Novel Regimen for Stage IV Pancreatic Cancer • • • A phase Ib/II study of 10 patients with advanced pancreatic cancer achieved responses in 80%, including 20% complete responses, using a regimen of albuminbound paclitaxel/gemcitabine plus cisplatin The use of cisplatin is based upon the finding of chromosomal aberrations that point to DNA-repair deficiency The phase II study is enrolling up to 25 patients Ms Jameson emphasized the need to strictly follow the clinical trial protocol “Our concern is that clinicians may take this regimen and modify it, which would not be advisable,” she said The investigators expect to have data from the phase II trial for presentation in 2017 If the phase II results are consistent with the initial findings, they hope to move this regimen forward The researchers wanted to credit their funding sources: the Seena Magowitz Foundation, which is dedicated to pancreatic research and treatment, as well as Mattress Firm, which collects public donations for pancreatic cancer research Stand Up To Cancer funded basic research associated with the project in collaboration with the Translational Genomics Research Institute ■ Disclosure: Ms Jameson is on the speakers bureau for Celgene Dr Borazanci reported no potential conflicts of interest References Jameson GS, Borazanci E, Poplin E, et al: High complete and partial response rate in a phase 1b pilot trial with cisplatin plus albumin-bound paclitaxel and gemcitabine in patients with advanced pancreatic cancer 2015 AACR Annual Meeting Abstract LB-003 Presented April 19, 2015 Von Hoff DD, Ervin T, Arena FP, et al: Increased survival in pancreatic cancer with nabpaclitaxel plus gemcitabine N Engl J Med 369:1691-1703, 2013 Conroy T, Desseigne F, Ychou M, et el: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer N Engl J Med 364:1817-1825, 2011 Ruiz C, Lenkiewicz E, Evers L, et al: Advancing a clinically relevant perspective of the clonal nature of care Proc Natl Acad Sci U S A 108:12054-12059, 2011 TGen-HonorHealth study: High rate of tumor shrinkage among pancreatic cancer patients Results of the Triplet Clinical Trial at HonorHealth Research Institute based on the TGen Triple research presented at ASCO-GI symposium in San Francisco The Translational Genomics Research Institute 25Apr2017 https://eurekalert.org/pub_releases/2017-04/ttgr-tsh042517.php SCOTTSDALE, Ariz - April 25, 2017 - Adding cisplatin to the standard gemcitabine/nabpaclitaxel drug treatment provided a very high rate of tumor shrinkage for patients with advanced pancreatic cancer, according to the results of a pilot clinical trial conducted by the HonorHealth Research Institute and the Translational Genomics Research Institute (TGen) These statistically significant and clinically meaningful improvements in overall response and survival rates resulted from a phase Ib/II clinical study performed at the HonorHealth Research Institute, a partnership of HonorHealth and TGen The results were presented during the 2017 Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology, in San Francisco Connecting a global network of more than 40,000 cancer professionals, the society serves as the leading resource for best practices in clinical oncology research and academic and community practices "After just three treatment cycles, we saw tumor markers plummet and some patients' tumors shrink significantly in just nine weeks," said Gayle Jameson, nurse practitioner and principal investigator of the clinical trial, who is highly encouraged by the response "After treatment, two patients had no evidence of disease and are alive over three years after starting this regimen This is very rare with traditional chemotherapy." Dr Daniel Von Hoff, TGen Distinguished Professor and Physician-in-Chief who devised the clinical trial, agreed: "Although a small study, the high response rate and landmark evolving median survival are very encouraging, and this regimen is being expanded for patients with stage IV pancreatic cancer." Dr Von Hoff also is chief scientific officer at the HonorHealth Research Institute Of the 24 evaluable patients (those whose response to a treatment could be measured because enough information was collected) who were enrolled in the study: • • • Eleven patients are still alive The median overall survival rate of 16.5 months exceeds the historical average survival of six-12 months with standard chemotherapy Seventeen of 24 patients 71 percent had a reduction in tumor size of at least 30 percent Two of those 17 patients had a complete response no detectable tumor This pilot clinical trial began in 2013 through a partnership between the HonorHealth Research Institute and TGen It was funded by Stand Up To Cancer, Mattress Firm, the Arizona Diamondbacks, and the Scottsdale-based Seena Magowitz Foundation Symptoms of pancreatic cancer usually not appear until the disease progresses to its late stages, making it difficult to treat Only about one in four patients survives more than a year after diagnosis, and fewer than 10 percent survive more than five years Pancreatic cancer this year will take the lives of more than 43,000 Americans, making it the nation's thirdleading cause of cancer-related death The results of this trial are encouraging and deserve additional testing prior to becoming a standard of care for patients with advanced pancreatic cancer Through research, the HonorHealth Research Institute and TGen aim to provide hope and a better chance for patients to live for years instead of months The current standard of care for advanced pancreatic cancer a combination of nabpaclitaxel and gemcitabine was developed by TGen and the HonorHealth Research Institute, and approved by the U.S Food and Drug Administration in 2013 About TGen Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results TGen is focused on helping patients with neurological disorders, cancer, and diabetes, through cutting edge translational research (the process of rapidly moving research towards patient benefit) TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process TGen is allied with City of Hope, a world-renowned independent research and cancer and diabetes treatment center This precision medicine alliance enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen For more information, visit: http://www.tgen.org Follow TGen on Facebook, LinkedIn and Twitter @TGen Media Contact: Steve Yozwiak, TGen Senior Science Writer, 602-343-8704, syozwiak@tgen.org About HonorHealth HonorHealth is a non-profit health system serving an area of 1.6 million people in the greater Phoenix area The network encompasses five acute-care hospitals, an extensive medical group, outpatient surgery centers, a cancer care network, clinical research, medical education, a foundation and community services with approximately 11,500 employees, 3,700 affiliated physicians and 3,100 volunteers HonorHealth was formed by a merger between Scottsdale Healthcare and John C Lincoln Health Network HonorHealth's mission is to improve the health and well-being of those we serve Learn more at HonorHealth.com Media Contact: Debbie Jacobson, 480-323-1384, debbie.jacobson@honorhealth.com Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system Below is the clinical trial description NabPaclitaxel+Cisplatin+Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDA) https://clinicaltrials.gov/show/NCT01893801 The recruitment status of this study is unknown The completion date has passed and the status has not been verified in more than two years Verified February 2014 by Pancreatic Cancer Research Team Recruitment status was: Recruiting Sponsor: Gayle Jameson Collaborators: Translational Genomics Research Institute Translational Drug Development Virgina G Piper Cancer Center - Clinical Trials Information provided by (Responsible Party): Gayle Jameson, Pancreatic Cancer Research Team ClinicalTrials.gov Identifier: NCT01893801 First received: July 2, 2013 Last updated: February 27, 2014 Last verified: February 2014 History of Changes • Full Text View • Tabular View • No Study Results Posted • Disclaimer • How to Read a Study Record Purpose The primary objective of this study is to determine the efficacy of nab-paclitaxel plus cisplatin plus gemcitabine for patients with metastatic pancreatic ductal adenocarcinoma (PDA) Condition Stage IV Pancreatic Cancer Intervention Drug: nab-paclitaxel Drug: Cisplatin Drug: gemcitabine Study Type: Interventional Study Design: Intervention Model: Single Group Assignment Phase Phase Phase Masking: Open Label Primary Purpose: Treatment Official Title: A Phase 1b/2 Pilot Trial of Nab-Paclitaxel Plus Cisplatin Plus Gemcitabine (Nabplagem) in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDA) Resource links provided by NLM: Drug Information available for: Cisplatin Paclitaxel Gemcitabine Gemcitabine hydrochloride U.S FDA Resources Further study details as provided by Pancreatic Cancer Research Team: Primary Outcome Measures: • Complete Response Rate [ Time Frame: yr ] The primary objectives of this study is to pursue treatment of 25 individual patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDA) to evaluate: Complete response rate as defined by computed tomography (CT) scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least > 2x ULN) We expect to accomplish this in > or = to 5% of patients When a complete response (CR) is documented, a confirmatory PET scan will be obtained If or more of 10 patients demonstrate a complete response (CR), study will continue to enroll to a total of 25 patients If intolerable adverse events or no clinical benefit are noted in the first patients, study will discontinue enrollment Secondary Outcome Measures: • Evaluate disease control rate [ Time Frame: weeks ] Evaluate disease control rate (CR, PR and SD at weeks) in patients with metastatic PDA • Evaluate treatment-related toxicities [ Time Frame: Over the course of the study ] Evaluate the treatment-related toxicities in this patient population • Evaluate the change in CA 19-9 or other biomarkers [ Time Frame: Over the course of the study ] Evaluate the change in CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) in this patient population Estimated Enrollment: 25 Study Start Date: May 2013 Estimated Study Completion Date: August 2014 Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure) Arms Assigned Interventions Experimental: nab-paclitaxel+Cisplatin+gemcitabine This is a phase Ib/II open-label, pilot study evaluating the preliminary efficacy and safety of nab-paclitaxel 125mb/m2, cisplatin 25mg/m2, and gemcitabine 1000mg/m2, all administered intravenously (IV) on Days and every 21 days until development of toxicity that is unacceptable in the opinion of the patient or the Investigator or upon disease progression Drug: nab-paclitaxel 25 mg/m2 given intravenously (IV) on days and of a 21 day cycle Other Name: Abraxane Drug: Cisplatin 25mg/m2 (or 50mg/m2) given intravenously (IV) on days and of a 21 day cycle Other Names: • cisplatinum • cisdiamminedichloroplatinum • CDDP Drug: gemcitabine 1000mg/m2 given intravenously (IV) on days and of a 21 day cycle Other Name: Gemzar Detailed Description: This is a phase 1b/2 open-label pilot study evaluating the preliminary efficacy and safety of nab-paclitaxel, cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma An individual cycle of therapy will be defined as Days and every 21 days Multiple cycles may be administered until the patient is withdrawn from therapy Overall response rates as well as individual categories of response (complete response-CR, partial response-PR, stable disease-SD and progressive disease-PD) will be determined using RECIST 1.1 Time-to-event endpoints, including progression free survival (PFS) and OS (overall survival) will be assessed using the Kaplan-Meier method Evaluation of stable disease at weeks will also be assessed Toxicity (adverse events) will be recorded using the NCI CTCAE (v4.0, May 2009) Eligibility Ages Eligible for Study: Sexes Eligible for Study: Accepts Healthy Volunteers: Criteria 18 Years and older (Adult, Senior) All No Inclusion Criteria: • • • • • • • Age >18 years of age; male or female Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma Capable of providing informed consent and complying with trial procedures Karnofsky Performance Status (KPS) of >/=70% Life expectancy >/=12 weeks Measurable tumor lesions according to RECIST 1.1 criteria Women must not be able to become pregnant (e.g post-menopausal for at least year, surgically sterile, or practicing adequate birth control methods) for the duration of the study Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating Both male and female patients of reproductive potential must agree to use a reliable method of birth control during the study Exclusion Criteria: • • • • • • • • • Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least months have elapsed since completion of the last dose and no lingering toxicities are present Palliative surgery and/or radiation treatment less than weeks prior to initiation of study treatment Exposure to any investigational agent within weeks prior to initiation of study treatment Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within weeks of Screening Visit) History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for >/= years Laboratory values: Screening serum creatinine > upper limits of normal (ULN); total bilirubin > ULN: alanine aminotransferase (ALT) and AST >/= 2.5 ULN or >/= 5.0 x ULN if liver metastases are present; absolute neutrophil count < 1,500/mm3, platelet concentration < 100,00/mm3, hematocrit level < 27% for females or < 30% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > 1.5 x ULN unless on therapeutic doses of warfarin Current, serious, clinically significant cardiac arrhythmias as determined by the Investigator History of HIV infection Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or anti-fungals • • Major surgery within weeks prior to initiation of study treatment Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results Any condition that is unstable and could jeopardize the patient's participation in the study Contacts and Locations Choosing to participate in a study is an important personal decision Talk with your doctor and family members or friends about deciding to join a study To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below For general information, see Learn About Clinical Studies Please refer to this study by its ClinicalTrials.gov identifier: NCT01893801 Contacts Contact: Amy Stoll-D'Astice, MS, CCRP (602) 358-8319 astoll@td2inc.com Locations United States, Arizona Scottsdale Health Care Scottsdale, Arizona, United States, 85260 Contact: Joyce Schaffer, MSN RN AOCNS 480-323-1339 Principal Investigator: Gayle S Jameson, MSN ACNP-BC Sub-Investigator: Ramesh K Ramanathan, MD Sub-Investigator: Daniel D Von Hoff, MD FACP Sub-Investigator: Katy B Schroeder, RN BSN OCN Recruiting joschaffer@shc.org United States, New Jersey Rutgers - Cancer Institute of New Jersey (CINJ) Recruiting New Brunswick, New Jersey, United States, 08901 Contact: Anjali Krishnan, RN 732-235-8996 warrieac@cinj.rutgers.edu Contact: Tatianna Zelinskaya 732-235-9837 zelinska@cinj.rutgers.edu Principal Investigator: Elizabeth Popllin, MD United States, Pennsylvania Vita Medical Associates, PC Recruiting Bethlehem, Pennsylvania, United States, 18015 Contact: Colleen Saitta, NP 610-866-0113 nurses@vitahemonc.org Contact: Gulyun Zhou, NP 610-866-0113 nurses@vitahemonc.org Principal Investigator: Anna A Niewiarowska, MD Sponsors and Collaborators Gayle Jameson Translational Genomics Research Institute Translational Drug Development Virgina G Piper Cancer Center - Clinical Trials Investigators Principal Investigator: More Information Gayle S Jameson, MSN ACNP-BC Scottsdale Health Care Additional Information: Additional information about the Pancreatic Cancer Research Team (PCRT) Non-profit Organization Related link Non-profit organization for pancreatic cancer research Publications: Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial J Clin Oncol 2011 Dec 1;29(34):4548-54 doi: 10.1200/JCO.2011.36.5742 Epub 2011 Oct 2013 Gastrointestinal Cancers Symposium Abstract LBA148 Presented January 25, 2013 Responsible Party: Gayle Jameson, Lead Principal Investigator, Pancreatic Cancer Research Team ClinicalTrials.gov Identifier: NCT01893801 Other Study ID Numbers: PCRT 12-001 Study First Received: July 2, 2013 Last Updated: February 27, 2014 History of Changes Keywords provided by Pancreatic Cancer Research Team: pancreatic cancer pancreatic adenocarcinoma Stage IV pancreatic cancer pancreas pancreatic Additional relevant MeSH terms: Pancreatic Neoplasms Adenocarcinoma Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Cisplatin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Paclitaxel Gemcitabine Albumin-Bound Paclitaxel Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs ClinicalTrials.gov processed this record on April 25, 2017