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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Pancreatic Cancer

Treatments: Biological: ipilimumab

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00112580

NCI-05-C-0141

CDR0000430666

NCI-P6557

MDX-010-24

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design