Clinical trial NCT00711191: A Study On An Immunostimulant Antibody In Combination With Chemotherapy For Advanced Cancer Of The Pancreas
Official title: A Phase 1 Dose Escalation Open Label Study Of CP-870,893 In Combination With Gemcitabine In Patients With Chemotherapy-Naïve Surgically Incurable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Neoplasm
Keywords: pancreas cancer; cancer of the pancreas; gemcitabine; chemotherapy; monoclonal antibody; immunotherapy; CD40
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2008-07-08
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to seek evidence that activation of certain cells of the immune system will be safe and well tolerated in combination with cytotoxic chemotherapy. Preliminary evidence of clinical anti-tumor activity will be sought.


Eligibility criteria: Inclusion Criteria:

* 1st-line surgically incurable cancer of the pancreas
* ECOG(Eastern Cooperative Oncology Group) performance status 0-1

Exclusion Criteria:

* Previous systemic therapy for pancreas cancer
* History of cancer-associated blood clots
* History of autoimmune disease

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Baseline up to Cycle 1 / Day 28
Secondary outcomes:
measure: Percentage of Participants With Objective Tumor Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: At the end of every even-numbered cycle (cycle=28 days) up to a maximum of 12 cycles and 4 to 6 weeks following initial documentation of response
measure: Overall Survival (OS)
timeFrame: Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
measure: Progression Free Survival (PFS)
timeFrame: Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
measure: Time to Progression
timeFrame: Monthly until death or 7.5 months after last participant was enrolled (up to January 2011)
measure: Maximum Serum Concentration (Cmax)
timeFrame: Cycle 1 / Day 3 pre-dose, 5 minutes after End of Infusion (EOI), and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Cycle 1 / Day 3 pre-dose, 5 minutes after EOI, and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles
measure: Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Pre-dose Concentration (CYTO0), Maximum Concentration (CTYOMAX)
timeFrame: Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI
measure: Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Time of Maximum Concentration (TCYTOMAX)
timeFrame: Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI
measure: Total and Neutralizing Human Antihuman Antibody (HAHA) Titer
timeFrame: Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles
measure: Change (Pre-dose to Post-dose) in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54, CD23, CD40, CD86, and Human Leukocyte Antigen (HLA-DR)
timeFrame: Cycle 1 / Day 1 and Cycle 1 / Day 8 prior to gemcitabine infusion and 6 and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-870893 infusion and 6, 24, and 48 hours after EOI
measure: 18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Imaging (MTD Expansion Cohort)
timeFrame: Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8
measure: Carbohydrate Antigen 19-9 (CA 19-9)
timeFrame: At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response
Other outcomes:
measure: Recommended Phase 2 Dose (RP2D) of CP-870893 in Participants With Advanced Pancreas Cancer
timeFrame: Baseline up to time of determination of maximum tolerated dose (MTD)
Locations:
city: Indianapolis
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O'Dwyer PJ, Vonderheide RH. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011 Mar 25;331(6024):1612-6. doi: 10.1126/science.1198443.