2nd-line, 3rd-line and Greater Metastatic Pancreatic Cancer Clinical Trial
— ECLIPSEOfficial title:
A Phase 2B, Randomized, Controlled, Multicenter, Open-Label Study of the Efficacy and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS 207 Compared to Chemotherapy or to CRS-207 Alone in Adults With Previously-Treated Metastatic Pancreatic Adenocarcinoma
| Verified date | May 2018 |
| Source | Aduro Biotech, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to chemotherapy or CRS-207 alone in adults with previously treated metastatic pancreatic adenocarcinoma
| Status | Completed |
| Enrollment | 303 |
| Est. completion date | August 23, 2016 |
| Est. primary completion date | January 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required, mixed histology is not allowed; subjects must have metastatic disease - 2nd line, 3rd line or greater - At least 18 years of age - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Anticipated life expectancy >12 weeks - For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. A barrier method of contraception must be employed by all subjects (male and female), regardless of other methods. - Have adequate organ function as defined by specified laboratory values Exclusion Criteria: - Allergy to both penicillin & sulfa or suspected hypersensitivity to granulocyte-macrophage colony stimulating factor (GM-CSF), dimethyl sulfoxide, fetal bovine serum, trypsin, yeast, glycerol or other component of the therapy options - Known history or evidence of brain metastases, immunodeficiency disease or immunocompromised state or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment - Have any evidence of hepatic cirrhosis or clinical or radiographic ascites - Have prosthetic heart valves, major implant or device placed in the last 12 months or history of infection with implant/device that cannot be easily removed - Rapidly progressing disease - Clinically significant and/or malignant pleural effusion - Received prior GVAX pancreas vaccine or CRS-207 - Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug, or planned surgery requiring general anesthesia - Infection with HIV or hepatitis B or C at screening - Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis - Pregnant or breastfeeding - Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen - Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Princess Margaret Hospital Princess Margaret Cancer Center | Toronto | Ontario |
| United States | University of Colorado Denver | Aurora | Colorado |
| United States | Johns Hopkins University | Baltimore | Maryland |
| United States | University of Virginia Health System | Charlottesville | Virginia |
| United States | University of Chicago Medical Center | Chicago | Illinois |
| United States | Duke University Medical Center Morris Cancer Center | Durham | North Carolina |
| United States | Baylor College of Medicine | Houston | Texas |
| United States | University California San Diego Moores Cancer Center | La Jolla | California |
| United States | University of Wisconsin - Carbone Cancer Center | Madison | Wisconsin |
| United States | University of Miami/Sylvester Cancer Center | Miami | Florida |
| United States | Vanderbilt University | Nashville | Tennessee |
| United States | Columbia University Medical Center | New York | New York |
| United States | Icahn School of Medicine at Mount Sinai | New York | New York |
| United States | University of Pittsburgh Medical Center Cancer Pavillion | Pittsburgh | Pennsylvania |
| United States | Providence Cancer Center | Portland | Oregon |
| United States | Mayo Clinic Rochester | Rochester | Minnesota |
| United States | Washington University | Saint Louis | Missouri |
| United States | University of California Mt Zion Comprehensive Cancer Center | San Francisco | California |
| United States | University of California Los Angeles | Santa Monica | California |
| United States | Scottsdale Healthcare Research Institute | Scottsdale | Arizona |
| United States | Virginia Mason Medical Center | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Aduro Biotech, Inc. | Johns Hopkins University |
United States, Canada,
Brockstedt DG, Giedlin MA, Leong ML, Bahjat KS, Gao Y, Luckett W, Liu W, Cook DN, Portnoy DA, Dubensky TW Jr. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13832-7. Epub 2004 Sep 13. — View Citation
Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, Tartakovsky I, Nemunaitis J, Le D, Sugar E, Hege K, Jaffee E. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008 Mar 1;14(5):1455-63. doi: 10.1158/1078-0432.CCR-07-0371. — View Citation
Le DT, Brockstedt DG, Nir-Paz R, Hampl J, Mathur S, Nemunaitis J, Sterman DH, Hassan R, Lutz E, Moyer B, Giedlin M, Louis JL, Sugar EA, Pons A, Cox AL, Levine J, Murphy AL, Illei P, Dubensky TW Jr, Eiden JE, Jaffee EM, Laheru DA. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res. 2012 Feb 1;18(3):858-68. doi: 10.1158/1078-0432.CCR-11-2121. Epub 2011 Dec 6. — View Citation
Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, Onners B, Uram JN, Laheru DA, Lutz ER, Solt S, Murphy AL, Skoble J, Lemmens E, Grous J, Dubensky T Jr, Brockstedt DG, Jaffee EM. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33. doi: 10.1200/JCO.2014.57.4244. Epub 2015 Jan 12. — View Citation
Lutz E, Yeo CJ, Lillemoe KD, Biedrzycki B, Kobrin B, Herman J, Sugar E, Piantadosi S, Cameron JL, Solt S, Onners B, Tartakovsky I, Choi M, Sharma R, Illei PB, Hruban RH, Abrams RA, Le D, Jaffee E, Laheru D. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011 Feb;253(2):328-35. doi: 10.1097/SLA.0b013e3181fd271c. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set) | OS was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs), with censoring at the date when 138 deaths were reached in the Primary Cohort in the FAS. Subjects without documentation of death at the time of final analysis were censored as of the date the subject was last known to be alive on/prior to the primary analysis data cut. | Subjects were followed from date of randomization to the date of death by any cause, whichever came first, assessed up to 32 months. Analysis conducted when 138 deaths reached in the Primary Cohort in the FAS. | |
| Primary | Primary Cohort: OS (All Data, FAS) | For all treated subjects, OS was calculated using KM methods with 95% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis data cut. | Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months. | |
| Primary | 2nd-line Cohort: OS (All Data, FAS) | For all treated subjects, OS was calculated using KM methods with 70% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis cut. 70% CIs were selected to provide an 80% probability to rule out differences in median survival less than -2.4 months between the 2nd-line Cohort: Chemotherapy arm and the 2nd-line Cohort: Cy/GVAX + CRS-207 and 2nd-line Cohort: CRS-207 arms, based upon the assumptions made in the statistical analysis plan (SAP). | Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months. | |
| Secondary | Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen | Safety was assessed based upon the number of adverse events (AEs) that occurred in the FAS of each treatment arm, including serious AEs and total AEs. Total AEs included both serious and non-serious AEs. | From the start of the first study drug administration on Day 1, Week 1, through 28 days after the last study drug dose, assessed up to 32 months from the date of randomization. |