MDX-010 in Treating Patients With Stage IV Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Trial of Single Agent Ipilimumab (MDX-010 Anti CTLA-4) for Subjects With Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: ipilimumab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: ipilimumab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From first dose to 3 weeks following the end of the treatment cycle, up to 24 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent pancreatic cancer, adenocarcinoma of the pancreas, stage IV pancreatic cancer