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

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Neoplasm
• Intervention / Treatment: Biological: monoclonal antibody; Drug: chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RP2D) of CP-870893 in Participants With Advanced Pancreas Cancer	Additional participants enrolled at MTD of CP-870893 to further characterize suitability for phase 2 testing. RP2D confirmed if ≤ 3 our of 12 participants in expansion cohort experience DLT in cycle 1.	Baseline up to time of determination of maximum tolerated dose (MTD)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: University of Pennsylvania

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: June 26, 2008
• First Submitted That Met QC Criteria: July 7, 2008
• First Posted (Estimate): July 8, 2008

Study Record Updates

• Last Update Posted (Estimate): December 24, 2013
• Last Update Submitted That Met QC Criteria: November 26, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: pancreas cancer; cancer of the pancreas; gemcitabine; chemotherapy; monoclonal antibody; immunotherapy; CD40
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: A5021005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No