Safety and Efficacy of Combination Listeria/GVAX Pancreas Vaccine in the Pancreatic Cancer Setting

NCT02004262 | Completed Phase 2 Results

• 1 other identifier: ADU-CL-04
• Study Type: interventional
• Target: 303
• Locations: 2 countries
• Sites: 21

Brief Summary

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

Conditions

2nd-line, 3rd-line and Greater Metastatic Pancreatic Cancer

Keywords

cancer; cancer vaccine; Listeria monocytogenes; Listeria-based vaccine; GVAX; cyclophosphamide; Cytoxan; immunotherapy; mesothelin

Outcome Measures

Primary Outcomes (3)

• 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 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.

• 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 Outcomes (1)

• Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen

  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.

Study Arms (6)

Primary Cohort: Cy/GVAX + CRS-207

EXPERIMENTAL

* 200 mg per square meter (mg/m\^2) cyclophosphamide (Cy) administered by intravenous (IV) infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (GVAX, 5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 colony forming units \[CFU\]) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16. * The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.

Biological: GVAX Pancreas Vaccine; Biological: CRS-207; Drug: cyclophosphamide

Primary Cohort: CRS-207

EXPERIMENTAL

* CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16. * The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.

Biological: CRS-207

Primary Cohort: Chemotherapy

ACTIVE COMPARATOR

* Investigator's choice of one of the following: gemcitabine (1000 mg/m\^2) administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle; capecitabine (1000 mg/m\^2) administered orally twice a day on Days 1 through 14 of a 21-day cycle; fluorouracil with or without leucovorin (2400 mg\^m2) administered by IV infusion over 46 hours on Days 1 and 15 of a 28-day cycle; irinotecan (150 mg/m\^2) administered by IV infusion on Days 1 and 15 of a 28-day cycle; or erlotinib (100 mg) administered orally once a day for a 21-day cycle. * The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.

Drug: Chemotherapy

2nd-line Cohort: Cy/GVAX + CRS-207

EXPERIMENTAL

* 200 mg/m\^2 Cy administered by IV infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16. * The 2nd-line Cohort comprised those subjects who received and failed 1 prior chemotherapy regimen administered for pancreatic cancer in the metastatic setting.

Biological: GVAX Pancreas Vaccine; Biological: CRS-207; Drug: cyclophosphamide

2nd-line Cohort: CRS-207

EXPERIMENTAL

* CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16. * The 2nd-line Cohort comprised those subjects who received and failed 1 prior chemotherapy regimen administered for pancreatic cancer in the metastatic setting.

Biological: CRS-207

2nd-line Cohort: Chemotherapy

ACTIVE COMPARATOR

* Investigator's choice of one of the following: gemcitabine (1000 mg/m\^2) administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle; capecitabine (1000 mg/m\^2) administered orally twice a day on Days 1 through 14 of a 21-day cycle; fluorouracil with or without leucovorin (2400 mg\^m2) administered by IV infusion over 46 hours on Days 1 and 15 of a 28-day cycle; irinotecan (150 mg/m\^2) administered by IV infusion on Days 1 and 15 of a 28-day cycle; or erlotinib (100 mg) administered orally once a day for a 21-day cycle. * The 2nd-line Cohort comprised those subjects who received and failed 1 prior chemotherapy regimen administered for pancreatic cancer in the metastatic setting.

Drug: Chemotherapy

Interventions

GVAX Pancreas Vaccine BIOLOGICAL

Also known as: GVAX

2nd-line Cohort: Cy/GVAX + CRS-207; Primary Cohort: Cy/GVAX + CRS-207

CRS-207 BIOLOGICAL

2nd-line Cohort: CRS-207; 2nd-line Cohort: Cy/GVAX + CRS-207; Primary Cohort: CRS-207; Primary Cohort: Cy/GVAX + CRS-207

Chemotherapy DRUG

Investigator's choice of one of the following commercially available products: gemcitabine; capecitabine; fluorouracil with or without leucovorin; irinotecan; or erlotinib.

2nd-line Cohort: Chemotherapy; Primary Cohort: Chemotherapy

cyclophosphamide DRUG

Also known as: Cytoxan

2nd-line Cohort: Cy/GVAX + CRS-207; Primary Cohort: Cy/GVAX + CRS-207

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required, mixed histology is not allowed; subjects must have metastatic disease
• nd 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aduro Biotech, Inc.: lead
• Johns Hopkins University: collaborator

Study Sites (21)

Scottsdale Healthcare Research Institute

Scottsdale, Arizona, 85258, United States

Location

University California San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

University of California Mt Zion Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Miami/Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center Morris Cancer Center

Durham, North Carolina, 27710, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

University of Pittsburgh Medical Center Cancer Pavillion

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37215, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Princess Margaret Hospital Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (6)

• 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. doi: 10.1073/pnas.0406035101. Epub 2004 Sep 13.

  PMID: 15365184 BACKGROUND

• 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.

  PMID: 22147941 BACKGROUND

• 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.

  PMID: 21217520 BACKGROUND

• 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.

  PMID: 18316569 BACKGROUND

• 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.

  PMID: 25584002 BACKGROUND

• Le DT, Picozzi VJ, Ko AH, Wainberg ZA, Kindler H, Wang-Gillam A, Oberstein P, Morse MA, Zeh HJ 3rd, Weekes C, Reid T, Borazanci E, Crocenzi T, LoConte NK, Musher B, Laheru D, Murphy A, Whiting C, Nair N, Enstrom A, Ferber S, Brockstedt DG, Jaffee EM. Results from a Phase IIb, Randomized, Multicenter Study of GVAX Pancreas and CRS-207 Compared with Chemotherapy in Adults with Previously Treated Metastatic Pancreatic Adenocarcinoma (ECLIPSE Study). Clin Cancer Res. 2019 Sep 15;25(18):5493-5502. doi: 10.1158/1078-0432.CCR-18-2992. Epub 2019 May 24.

  PMID: 31126960 DERIVED

Related Links

• The Pancreatic Cancer Action Network's Patient \& Liaison Services (PALS) program provides patients and families with information and resources at no cost. Visit www.pancan.org, call 877-272-6226 or email pals@pancan.org for information.

MeSH Terms

Conditions

Neoplasms

Interventions

Drug Therapy; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

A high number of patients in the chemotherapy arm withdrew from the study before receiving treatment. This high dropout rate may have an impact on interpretation of the study results.

Results Point of Contact

• Title: Corporate Communications
• Organization: Aduro Biotech, Inc.

510-848-4400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: December 9, 2013
• Study Start: February 5, 2014
• Primary Completion: January 1, 2016
• Study Completion: August 23, 2016
• Last Updated: June 4, 2018
• Results First Posted: May 3, 2018

Record last verified: 2018-05

Locations

CA (1); US (20)