A Study On An Immunostimulant Antibody In Combination With Chemotherapy For Advanced Cancer Of The Pancreas

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pancreatic Neoplasm

Intervention / Treatment
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* Biological: monoclonal antibody
* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br> | Biological: monoclonal antibody<br>* CP-870,893 intravenous administration [IV] on day 3 of 4-week cycles<br>Drug: chemotherapy<br>* gemcitabine 1000 mg/m^2 intravenous administration [IV] q week [wk]x3 of 4-week cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Any of the following during first cycle of treatment and attributable to CP-870893: afebrile Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) ≥7 days or Gr 3 or 4 neutropenia associated with fever (1 oral temperature >38.5 degrees Celsius (C) or 3 oral temperatures >38.0 degrees C in a 24-hour period); Gr 4 thrombocytopenia or Gr 3 thrombocytopenia associated with bleeding; Gr 4 lymphopenia, if coupled with clinical consequence (such as, opportunistic infection) or any other Gr 3 hematological adverse events; ≥Gr 3 non-hematologic toxicities (except alopecia). | Baseline up to Cycle 1 / Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Tumor Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. | 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 | 
| Overall Survival (OS) | OS is time from baseline to death from any cause. Participants last known to be alive were censored at the date of last contact. | Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011) | 
| Progression Free Survival (PFS) | PFS is time from baseline to first progression (Prog) or death from any cause. Participants last known to be alive, had not started a new (non-protocol) cancer treatment, were Prog-free, and who had a baseline and ≥1 on-study disease assessment were censored at date of last objective disease assessment that verified lack of Prog. Participants who were off treatment prior to Prog and who had no on-study disease assessment were also censored. Prog: ≥20% increase in sum of longest dimension (LD) of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions. | Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011) | 
| Time to Progression | Disease progression defined as ≥20% increase in sum LD of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions. Criteria for progression also included unequivocal progression of existing nontarget lesions. | Monthly until death or 7.5 months after last participant was enrolled (up to January 2011) | 
| Maximum Serum Concentration (Cmax) |  | 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 | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the serum concentration time-curve from time zero to the last measured concentration. AUClast analyzed using a noncompartmental approach to estimate individual participant values. | 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 | 
| Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Pre-dose Concentration (CYTO0), Maximum Concentration (CTYOMAX) | An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. Change calculated as mean of pre-dose and maximum post-dose values. | 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 | 
| Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Time of Maximum Concentration (TCYTOMAX) | An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. Change calculated as mean of pre-dose and maximum post-dose values. | 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 | 
| Total and Neutralizing Human Antihuman Antibody (HAHA) Titer | HAHA assessed as an indicator of immunogenicity to CP-870893. | Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles | 
| 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) | Assess the ability of PF-870893 to activate B-cells and HLA-DR which are involved in the production of antibodies. Change calculated as mean of pre-dose and post-dose values. Positive values indicate greater presence of cells associated with antibody production. | 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 | 
| 18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Imaging (MTD Expansion Cohort) | FDG PET assessment to characterize and monitor tumors before and after study treatment; measured as a standardized uptake value (SUV). A reduction in SUV from baseline for at least 1 tumor may indicate a positive metabolic response to treatment. | Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8 | 
| Carbohydrate Antigen 19-9 (CA 19-9) | CA 19-9 or sialylated Lewis (a) antigen (a tumor marker). Values higher than 37 units per milliliter (U/ml) considered abnormal; higher values usually indicate greater presence of disease. | At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreas cancer; cancer of the pancreas; gemcitabine; chemotherapy; monoclonal antibody; immunotherapy; CD40