Clinical trial NCT00112580: MDX-010 in Treating Patients With Stage IV Pancreatic Cancer That Cannot Be Removed By Surgery
Official title: Phase II Trial of Single Agent Ipilimumab (MDX-010 Anti CTLA-4) for Subjects With Locally Advanced or Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: recurrent pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-06-03
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR)
timeFrame: From first dose to 3 weeks following the end of the treatment cycle, up to 24 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
state: Maryland
city: Bethesda
country: United States
facility: NCI - Surgery Branch
state: Maryland
Study officials:
affiliation: NCI - Surgery Branch
name: Steven A. Rosenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010 Oct;33(8):828-33. doi: 10.1097/CJI.0b013e3181eec14c.