Ipilimumab and Gemcitabine Hydrochloride in Treating Patients With Stage III-IV or Recurrent Pancreatic Cancer That Cannot Be Removed by Surgery

Brief summary public domain (ClinicalTrials.gov)

This phase I trial studies the side effects and best dose of ipilimumab when given together with gemcitabine hydrochloride in treating patients with stage III-IV or recurrent pancreatic cancer that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to kill tumor cells or stop them from growing. Giving monoclonal antibody therapy together with chemotherapy may kill more tumor cells.

Detailed description public domain (ClinicalTrials.gov)

OUTLINE: This is a dose-escalation study of ipilimumab. INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes in weeks 1, 4, 7, and 10, and gemcitabine hydrochloride IV over 30 minutes in weeks 1-7 and 9-11. MAINTENANCE: Beginning in week 22, patients receive ipilimumab IV over 90 minutes once every 12 weeks and gemcitabine hydrochloride IV over 30 minutes once weekly for 3 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment modifications may apply according to response. After completion of study treatment, patients are followed up monthly for 6 months and then every 3 months.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Dose Limiting Toxicities (DLTs) Seen in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination in Order to Define the Maximum Tolerated Dose (MTD) [During the 12 weeks of Induction Therapy]. Number, DLTs. Number of DLTS seen in cohort: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 0; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 0; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 2. Number of AST increase DLTs seen in cohort: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 0; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 0; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 1. Number of diarrhea DLTs seen in cohort: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 0; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 0; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 1. Analysis, Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg vs Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg vs Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg: other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Rate Using Immune-related Response Criteria (irRC) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination [Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10]. Count Of Participants, Participants. irCR: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 0; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 0; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 0; Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=8): 0. irPR: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 0; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 1; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 1; Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=8): 1. irSD: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 2; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 0; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 3; Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=8): 2. irPD: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 1; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 3; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 1; Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=8): 3. NE - Death: Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 0; Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=4): 0; Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 1; Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg (n=8): 2.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Time to Progression Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination Who Progress While on Treatment [Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination [Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10]. Median, months (95% Confidence Interval). Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 3.3859 (2.5970 to 8.0868); Cohort 2/Expansion Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg (n=12): 2.5312 (0.7890 to 4.8323); Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=6): 3.8626 (0.7561 to 22.4195).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination [Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10]. Median, months (95% Confidence Interval). Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg (n=3): 5.3254 (5.0953 to 9.5661); Cohort 2/Expansion Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg (n=12): 5.7199 (1.6108 to 22.8139); Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg (n=8): 8.9908 (0.7561 to 30.0460).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Recovery of Tumor Immune Surveillance: T-cell Response to Defined Pancreatic Cancer Tumor Antigens [Prior to ipilimumab infusion at weeks 1, 4, 7, and 10, and then every 12 weeks starting at week 13 where range of cycles including induction cycle was 0-10 (Induction cycle = 12 weeks, maintenance cycle = 28 days)].