Pancreatic Cancer
Conditions
Keywords
pancreatic cancer, vaccine, immunotherapy, antibody, CTLA-4
Brief summary
Research Hypothesis: Ipilimumab (an antibody that blocks negative signals to T cells) administered alone or in combination with a pancreatic cancer vaccine (allogeneic pancreatic tumor cells transfected with a GM-CSF gene), has an acceptable safety profile in subjects with locally advanced, unresectable or metastatic pancreatic adenocarcinoma. Primary Objective: To determine the safety profile of ipilimumab alone or in combination with a pancreatic cancer vaccine in subjects with locally advanced, unresectable or metastatic pancreatic adenocarcinoma. Secondary Objectives: * To estimate overall survival (OS) which will serve as the primary efficacy signal. * To explore an association of T cell responses and immunological responses with OS in patients receiving treatment. * To estimate overall response rate (ORR), immune related best overall response rate (irBOR), progression free survival (PFS), and duration of response in patients receiving treatment. * To explore an association between immune-related adverse events (IRAEs) and ORR. * To measure tumor marker kinetics (CA 19-9) in patients receiving treatment.
Interventions
DRUGIpilimumab
Ipilimumab (10mg/kg) will be administered intravenously at weeks 1, 4, 7 and 10. Subjects will also be offered maintenance phase dosing every 12 weeks.
BIOLOGICALPancreatic Cancer Vaccine
The Pancreatic Cancer Vaccine (5E8 cells) will be administered intradermally at weeks 1, 4, 7 and 10. Subjects will also be offered maintenance phase dosing every 12 weeks.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
1. Documented cancer of the pancreas who have failed (or are not candidates for) standard therapy 2. ECOG Performance Status of 0 to 1 3. Adequate organ function as defined by study-specified laboratory tests 4. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug 5. Signed informed consent form 6. Willing and able to comply with study procedures
Exclusion criteria
1. Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions 2. Clinical metabolic or laboratory abnormalities defined as Grade 3 or 4 of the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 3. Systemically active steroids 4. Another investigational product within 28 days prior to receiving study drug 5. Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug 6. Infection with HIV, hepatitis B or C at screening 7. Pregnant or lactating 8. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Experiencing an Unacceptable Toxicity | 4 years | Unacceptable toxicity is defined as drug related \>grade 4 AEs or grade 3 AEs including IRAEs not improving to \< grade 2 under therapy within 2 weeks. In addition, \> grade 2 eye pain or reduction of visual acuity that does not respond to topical therapy and does not improve to \< grade 1 severity within 2 weeks of starting therapy, or requires systemic therapy is an unacceptable toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 4 years | OS will be measured from date of randomization until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). |
| Overall Response Rate (ORR) | 6 months | ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) during the first 6 months of treatment. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. |
| Immune Related Best Overall Response Rate (irBOR) | 4 years | Immune Related Best Overall Response (BOR) is the best response recorded from the start of the study treatment until the disease progression/recurrence based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Estimation based on the Kaplan-Meier curve. |
| Progression Free Survival (PFS) | 6 months | PFS is defined as the number of months from the date of randomization to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Ipilimumab Alone Ipilimumab alone | 15 |
| Arm 2: Ipilimumab + Pancreatic Cancer Vaccine Ipilimumab + Pancreatic Cancer Vaccine | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Arm 2: Ipilimumab + Pancreatic Cancer Vaccine | Arm 1: Ipilimumab Alone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Age, Continuous | 61.9 years STANDARD_DEVIATION 8.9 | 62.3 years STANDARD_DEVIATION 7.8 | 62.1 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 15 | 15 / 15 |
| serious Total, serious adverse events | 3 / 15 | 1 / 15 |
Outcome results
Primary
Percent of Patients Experiencing an Unacceptable Toxicity
Unacceptable toxicity is defined as drug related \>grade 4 AEs or grade 3 AEs including IRAEs not improving to \< grade 2 under therapy within 2 weeks. In addition, \> grade 2 eye pain or reduction of visual acuity that does not respond to topical therapy and does not improve to \< grade 1 severity within 2 weeks of starting therapy, or requires systemic therapy is an unacceptable toxicity.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Ipilimumab Alone | Percent of Patients Experiencing an Unacceptable Toxicity | 6.67 Percentage of Participants |
| Arm 2: Ipilimumab + Pancreatic Cancer Vaccine | Percent of Patients Experiencing an Unacceptable Toxicity | 6.67 Percentage of Participants |
Secondary
Immune Related Best Overall Response Rate (irBOR)
Immune Related Best Overall Response (BOR) is the best response recorded from the start of the study treatment until the disease progression/recurrence based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Estimation based on the Kaplan-Meier curve.
Time frame: 4 years
Secondary
Overall Response Rate (ORR)
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) during the first 6 months of treatment. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Time frame: 6 months
Secondary
Overall Survival (OS)
OS will be measured from date of randomization until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).
Time frame: 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Ipilimumab Alone | Overall Survival (OS) | 3.6 Months |
| Arm 2: Ipilimumab + Pancreatic Cancer Vaccine | Overall Survival (OS) | 5.7 Months |
Secondary
Progression Free Survival (PFS)
PFS is defined as the number of months from the date of randomization to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Time frame: 6 months