Metastatic Pancreatic Cancer
Conditions
Keywords
Cancer, Cancer vaccine, Listeria monocytogenes, Listeria-based vaccines, GVAX, Cyclophosphamide, Cytoxan, T regulatory cells, Heterologous Prime-Boost, Immunotherapy, Mesothelin, Pancreatic cancer
Brief summary
Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to GVAX pancreas vaccine (with cyclophosphamide) alone in adults who have failed or refused prior treatment for metastatic pancreatic cancer.
Interventions
Sponsors
Johns Hopkins University
Aduro Biotech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required. (Subjects with mixed histology will be included if the predominant component is adenocarcinoma. Subjects must have metastatic disease.) * Have received or refused at least one chemotherapy regimen * At least 18 years of age * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Anticipated life expectancy of \>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.) * Be willing and able to give written informed consent, and be able to comply with all study procedures * Have adequate organ function as defined by specified laboratory values
Exclusion criteria
* Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions * Known history or evidence of brain metastases * Have any evidence of hepatic cirrhosis or clinical or radiographic ascites * Have clinically significant and/or malignant pleural effusion * Known or suspected hypersensitivity to any component of GVAX Pancreas vaccine or CRS-207, or known allergy to both penicillin and sulfa * Received an investigational product within 28 days of study treatment or planned to receive within 28 days after vaccine administration * Used any systemic steroids within 28 days of study treatment * Use more than 3 g/d of acetaminophen * Prosthetic joint or other artificial implant or device that cannot be easily removed (there are some exceptions) * 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 * Any immunodeficiency disease or immunocompromised state or active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment * Be 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Subjects Receiving Test Treatments (FAS) | Subjects were followed from the date of randomization to the date of death or discontinuation, whichever came first, assessed up to 60 months. | For all treated subjects, OS was defined as the time between the date of randomization and the date of death or censoring, and was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects without documentation of death at the time of the final analysis were censored using the date the subject was last known to be alive. Per the study protocol, following an Interim Analysis (IA), subjects in the Cy/GVAX arm were offered rollover to Cy/GVAX + CRS-207 arm. 3 subjects rolled over to the Cy/GVAX + CRS-207 arm (rollover subjects). These rollover subjects were censored at the day prior to the first rollover treatment dose date, and were included for analysis in the Cy/GVAX arm. Additionally, 2 subjects originally treated per the Cy/GVAX + CRS-207 arm discontinued treatment and entered follow-up, but following IA were re-treated per the Cy/GVAX + CRS-207 arm regimen. Data from these re-treated subjects were included in the Cy/GVAX + CRS-207 arm analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen | Starting with administration of first investigational drug product through 28 days after final study treatment, assessed up to 60 months from the date of randomization. | 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. AEs reported for the Cy/GVAX + CRS-207 arm (FAS) include the 61 treated subjects initially assigned to this arm plus AEs occurring on/after the first rollover dose date for the 3 Cy/GVAX rollover subjects. AEs reported for the Cy/GVAX arm (FAS) include treated subjects initially assigned to this arm but exclude AEs for rollover subjects occurring on/after the first rollover dose date. |
Countries
United States
Participant flow
Recruitment details
This study enrolled subjects with malignant metastatic adenocarcinoma of the pancreas who had received or refused at least one prior chemotherapy regimen. Study was conducted in the United States at 10 medical centers; however, 1 center did not enroll any subjects. The last subject completed the study in February 2017.
Pre-assignment details
Participants screened over a 28-day period.
Participants by arm
| Arm | Count |
|---|---|
| Cy/GVAX + CRS-207 200 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. | 61 |
| Cy/GVAX 200 mg/m\^2 Cy administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16; GVAX pancreas vaccine (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1, 4, 7, 10, 13, 16. | 29 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 59 | 28 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 1 | 1 |
Baseline characteristics
| Characteristic | Cy/GVAX + CRS-207 | Cy/GVAX | Total |
|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 9.14 | 63.9 years STANDARD_DEVIATION 9.29 | 63.8 years STANDARD_DEVIATION 9.13 |
| Sex: Female, Male Female | 27 Participants | 10 Participants | 37 Participants |
| Sex: Female, Male Male | 34 Participants | 19 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 64 / 64 | 29 / 29 |
| serious Total, serious adverse events | 29 / 64 | 10 / 29 |
Outcome results
Primary
Overall Survival (OS) in Subjects Receiving Test Treatments (FAS)
For all treated subjects, OS was defined as the time between the date of randomization and the date of death or censoring, and was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects without documentation of death at the time of the final analysis were censored using the date the subject was last known to be alive. Per the study protocol, following an Interim Analysis (IA), subjects in the Cy/GVAX arm were offered rollover to Cy/GVAX + CRS-207 arm. 3 subjects rolled over to the Cy/GVAX + CRS-207 arm (rollover subjects). These rollover subjects were censored at the day prior to the first rollover treatment dose date, and were included for analysis in the Cy/GVAX arm. Additionally, 2 subjects originally treated per the Cy/GVAX + CRS-207 arm discontinued treatment and entered follow-up, but following IA were re-treated per the Cy/GVAX + CRS-207 arm regimen. Data from these re-treated subjects were included in the Cy/GVAX + CRS-207 arm analysis.
Time frame: Subjects were followed from the date of randomization to the date of death or discontinuation, whichever came first, assessed up to 60 months.
Population: Analysis conducted for the FAS of each study arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cy/GVAX + CRS-207 | Overall Survival (OS) in Subjects Receiving Test Treatments (FAS) | 6.28 months |
| Cy/GVAX | Overall Survival (OS) in Subjects Receiving Test Treatments (FAS) | 4.07 months |
Secondary
To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 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. AEs reported for the Cy/GVAX + CRS-207 arm (FAS) include the 61 treated subjects initially assigned to this arm plus AEs occurring on/after the first rollover dose date for the 3 Cy/GVAX rollover subjects. AEs reported for the Cy/GVAX arm (FAS) include treated subjects initially assigned to this arm but exclude AEs for rollover subjects occurring on/after the first rollover dose date.
Time frame: Starting with administration of first investigational drug product through 28 days after final study treatment, assessed up to 60 months from the date of randomization.
Population: Analysis conducted for the FAS of each study arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cy/GVAX + CRS-207 | To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen | Serious AEs | 29 Participants |
| Cy/GVAX + CRS-207 | To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen | Total AEs | 64 Participants |
| Cy/GVAX | To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen | Serious AEs | 10 Participants |
| Cy/GVAX | To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen | Total AEs | 29 Participants |