A Study On An Immunostimulant Antibody In Combination With Chemotherapy For Advanced Cancer Of The Pancreas
This study has been completed.
Sponsor:
Pfizer
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00711191
First received: June 26, 2008
Last updated: June 5, 2012
Last verified: June 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Pancreatic Neoplasm |
Biological: monoclonal antibody Drug: chemotherapy |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Pfizer:
Primary Outcome Measures:
- Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline up to Cycle 1 / Day 28 ] [ Designated as safety issue: Yes ]
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).
Secondary Outcome Measures:
- Percentage of Participants With Objective Tumor Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 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 ] [ Designated as safety issue: No ]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.
- Overall Survival (OS) [ Time Frame: Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011) ] [ Designated as safety issue: Yes ]OS is time from baseline to death from any cause. Participants last known to be alive were censored at the date of last contact.
- Progression Free Survival (PFS) [ Time Frame: Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011) ] [ Designated as safety issue: No ]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.
- Time to Progression [ Time Frame: Monthly until death or 7.5 months after last participant was enrolled (up to January 2011) ] [ Designated as safety issue: No ]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.
- Maximum Serum Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ] [ Designated as safety issue: No ]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.
- Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Pre-dose Concentration (CYTO0), Maximum Concentration (CTYOMAX) [ Time Frame: 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 ] [ Designated as safety issue: No ]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.
- Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Time of Maximum Concentration (TCYTOMAX) [ Time Frame: 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 ] [ Designated as safety issue: No ]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.
- Total and Neutralizing Human Antihuman Antibody (HAHA) Titer [ Time Frame: Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles ] [ Designated as safety issue: Yes ]HAHA assessed as an indicator of immunogenicity to CP-870893.
- 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) [ Time Frame: 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 ] [ Designated as safety issue: No ]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.
- 18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Imaging (MTD Expansion Cohort) [ Time Frame: Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8 ] [ Designated as safety issue: No ]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.
- Carbohydrate Antigen 19-9 (CA 19-9) [ Time Frame: At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response ] [ Designated as safety issue: No ]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.
| Enrollment: | 22 |
| Study Start Date: | June 2008 |
| Study Completion Date: | January 2011 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: single arm |
Biological: monoclonal antibody
CP-870,893 intravenous administration [IV] on day 3 of 4-week cycles
Drug: chemotherapy
gemcitabine 1000 mg/m^2 intravenous administration [IV] q week [wk]x3 of 4-week cycles
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00711191
Locations
| United States, Indiana | |
| Pfizer Investigational Site | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Pennsylvania | |
| Pfizer Investigational Site | |
| Philadelphia, Pennsylvania, United States, 19104 | |
Sponsors and Collaborators
Pfizer
University of Pennsylvania
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
More Information
Additional Information:
No publications provided by Pfizer
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT00711191 History of Changes |
| Other Study ID Numbers: | A5021005 |
| Study First Received: | June 26, 2008 |
| Results First Received: | May 3, 2012 |
| Last Updated: | June 5, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Pfizer:
|
pancreas cancer; cancer of the pancreas; gemcitabine; chemotherapy; monoclonal antibody; immunotherapy; CD40 |
Additional relevant MeSH terms:
|
Neoplasms Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Antibodies Immunoglobulins Antibodies, Monoclonal Gemcitabine Pancrelipase Immunologic Factors |
Physiological Effects of Drugs Pharmacologic Actions Gastrointestinal Agents Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on May 16, 2013