NCT02004262已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 303
- 试验地点
- 21
- 主要终点
- Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: GVAX Pancreas Vaccine (Biological)
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.
干预措施: CRS-207 (Biological)
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.
干预措施: cyclophosphamide (Drug)
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.
干预措施: CRS-207 (Biological)
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.
干预措施: Chemotherapy (Drug)
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.
干预措施: GVAX Pancreas Vaccine (Biological)
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.
干预措施: CRS-207 (Biological)
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.
干预措施: cyclophosphamide (Drug)
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.
干预措施: CRS-207 (Biological)
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.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set)
时间窗: 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.
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.
Primary Cohort: OS (All Data, FAS)
时间窗: 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.
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.
2nd-line Cohort: OS (All Data, FAS)
时间窗: 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.
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).
次要结局
- 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.)
研究者
研究点 (21)
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