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

Phase 1

Completed

• Conditions: Pancreatic Neoplasm
• Interventions: Biological: monoclonal antibody; Drug: chemotherapy

• Registration Number: NCT00711191
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2008-06
• Study First Submitted: 2008-06-26
• Study First Submitted QC: 2008-07-07
• Study First Posted: 2008-07-08
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Results First Submitted: 2012-05-03
• Results First Submitted QC: 2012-05-03
• Results First Posted: 2012-06-06
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-26
• Last Update Posted: 2013-12-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm	monoclonal antibody	-
single arm	chemotherapy	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities (DLTs)	Baseline up to Cycle 1 / Day 28	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

Name	Time	Method
Percentage of Participants With Objective Tumor Response According to Response Evaluation Criteria in Solid Tumors (RECIST)	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	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)	Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)	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)	Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)	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	Monthly until death or 7.5 months after last participant was enrolled (up to January 2011)	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)	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)	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	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)	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	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)	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	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	Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles	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)	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	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)	Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8	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)	At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response	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.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇺🇸 Philadelphia, Pennsylvania, United States