Patient case: 50-year-old male with pancreatic cancer; genetic feature: BRCA2

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

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.

Eligibility: 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)

Relevance to patient case: not relevant