Pancreatic Cancer
Conditions
Keywords
recurrent pancreatic cancer, adenocarcinoma of the pancreas, stage IV pancreatic cancer
Brief summary
RATIONALE: Biological therapies, such as MDX-010, may stimulate the immune system in different ways and stop tumor cells from growing. PURPOSE: This phase II trial is studying how well MDX-010 works in treating patients with stage IV pancreatic cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * Determine clinical response (partial and complete responses) in patients with unresectable stage IV (locally or distantly metastatic) pancreatic adenocarcinoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010). Secondary * Determine whether observed responses correlate with the incidence of autoimmunity in patients treated with this drug. OUTLINE: This is an open-label study. Patients are stratified according to status of disease (locally vs distantly metastatic). Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on days 0, 21, 42, and 63. Treatment repeats every 84 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression after achieving a partial response or complete response receive 2 additional courses of therapy. After completion of study treatment, patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 42-82 patients (21-41 per stratum) will be accrued for this study within 2-4 years.
Interventions
BIOLOGICALipilimumab
Sponsors
National Cancer Institute (NCI)
Bristol-Myers Squibb
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed pancreatic adenocarcinoma * Stage IV disease * Locally (invasion of adjacent structures, including mesenteric arteries or organs) or distantly metastatic disease * Unresectable disease * Pancreatic adenocarcinoma with intraductal papillary mucinous neoplasm allowed * The following diagnoses are not allowed: * Acinar cell carcinoma * Pancreaticoblastoma * Malignant cystic neoplasms * Endocrine neoplasms * Squamous cell carcinoma * Vater and periampullary duodenal or common bile duct malignancies * Clinically evaluable disease with ≥ 1 site of measurable disease * Biliary or gastric outlet obstruction allowed provided it is effectively drained by endoscopic, operative, or interventional means * Pancreatic, biliary, or enteric fistulae allowed provided they are controlled with an appropriate drain PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * At least 3 months Hematopoietic * WBC ≥ 2,500/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL * Hematocrit ≥ 27% Hepatic * Hepatitis B surface antigen negative * Hepatitis C virus antibody negative OR * Hepatitis C RNA negative by polymerase chain reaction Renal * Creatinine \< 2.0 mg/dL Immunologic * HIV negative * No history of or active autoimmune disease, including uveitis or autoimmune inflammatory eye disease * No active uncontrolled infection Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix * No underlying medical condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) Chemotherapy * At least 3 weeks since prior chemotherapy for pancreatic adenocarcinoma and recovered * No concurrent chemotherapy Endocrine therapy * More than 4 weeks since prior corticosteroids * No concurrent systemic or topical corticosteroids Radiotherapy * At least 3 weeks since prior radiotherapy for pancreatic adenocarcinoma and recovered Surgery * See Disease Characteristics Other * At least 3 weeks since other prior therapy for pancreatic adenocarcinoma and recovered * No concurrent immunosuppressants (e.g., cyclosporin or its analog)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) | From first dose to 3 weeks following the end of the treatment cycle, up to 24 weeks. | Percentage of participants who achieved Complete Response (CR) or Partial Response (PR) according to RECIST criteria. Particularly, CR is defined as disappearance of all target lesions, while PR is defined as at least a 30% decrease n the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. |
Countries
United States
Participant flow
Pre-assignment details
27 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Locally Advanced Cohort Participants with locally advanced pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks. | 8 |
| Metastatic Cohort Participants with metastatic pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks. | 19 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Disease progression | 5 | 16 |
| Overall Study | Participant withdrew consent | 2 | 1 |
Baseline characteristics
| Characteristic | Locally Advanced Cohort | Metastatic Cohort | Total |
|---|---|---|---|
| Age, Continuous | 58.3 Years STANDARD_DEVIATION 6.48 | 51.5 Years STANDARD_DEVIATION 9.81 | 53.5 Years STANDARD_DEVIATION 9.36 |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 18 Participants | 26 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 12 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 27 |
| other Total, other adverse events | 26 / 27 |
| serious Total, serious adverse events | 20 / 27 |
Outcome results
Primary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR)
Percentage of participants who achieved Complete Response (CR) or Partial Response (PR) according to RECIST criteria. Particularly, CR is defined as disappearance of all target lesions, while PR is defined as at least a 30% decrease n the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time frame: From first dose to 3 weeks following the end of the treatment cycle, up to 24 weeks.
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Locally Advanced Cohort | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) | 0 Percent of Participants |
| Metastatic Cohort | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) | 0 Percent of Participants |