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

This study has been completed.
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00711191
First received: June 26, 2008
Last updated: November 26, 2013
Last verified: November 2013
  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 Hoffmann-La Roche:

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.


Other Outcome Measures:
  • Recommended Phase 2 Dose (RP2D) of CP-870893 in Participants With Advanced Pancreas Cancer [ Time Frame: Baseline up to time of determination of maximum tolerated dose (MTD) ] [ Designated as safety issue: Yes ]
    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.


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Hoffmann-La Roche
University of Pennsylvania
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
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: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoffmann-La Roche:
pancreas cancer; cancer of the pancreas; gemcitabine; chemotherapy; monoclonal antibody; immunotherapy; CD40

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014