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

Aduro Biotech

Status and phase: Completed; Phase 2

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

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02004262

ADU-CL-04

Details and patient eligibility

About

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

Enrollment: 303 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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303 participants in 6 patient groups

Primary Cohort: Cy/GVAX + CRS-207

Experimental group

Description:

* 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.

Treatment:

Drug: cyclophosphamide

Biological: GVAX Pancreas Vaccine

Biological: CRS-207

Primary Cohort: CRS-207

Experimental group

Description:

* 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.

Treatment:

Biological: CRS-207

Primary Cohort: Chemotherapy

Active Comparator group

Description:

* 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.

Treatment:

Drug: Chemotherapy

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

Experimental group

Description:

* 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.

Treatment:

Drug: cyclophosphamide

Biological: GVAX Pancreas Vaccine

Biological: CRS-207

2nd-line Cohort: CRS-207

Experimental group

Description:

* 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.

Treatment:

Biological: CRS-207

2nd-line Cohort: Chemotherapy

Active Comparator group

Description:

* 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.

Treatment:

Drug: Chemotherapy