Dose Finding Study Of CP-870,893, An Immune System Stimulating Antibody, In Combination With Paclitaxel And Carboplatin For Patients With Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00607048
First received: January 22, 2008
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

This is a dose-finding study; therefore, there is no hypothesis testing


Condition Intervention Phase
Neoplasms
Drug: Paclitaxel + Carboplatin + CP-870,893
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study Of CP- 870,893 In Combination With Paclitaxel And Carboplatin In Patients With Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) [ Time Frame: Schedule (Sch) A Cycle 1 / Day 3 or Schedule B Cycle 1 / Day 8 up to Cycle 1 / Day 21 ] [ Designated as safety issue: Yes ]
    Any of the following during first cycle of treatment and attributable to CP-870893: Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for ≥7 days; Gr 3 or 4 febrile neutropenia (ANC <1000/mm^3, fever ≥38.5 degrees Celsius; platelets ≤25,000 cells/mm^3); ≥Gr 3 non-hematological adverse event despite optimal supportive care; ≥Gr 3 cytokine release syndrome or acute infusion reaction; failure to recover to Gr <1 toxicity after delaying next cycle by maximum of 2 weeks; Day 3 or 8 ANC <1000 cells/mm^3 or platelets <80000 cells/mm^3, or non-hematologic toxicity ≥Gr 2.


Secondary Outcome Measures:
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours (hrs) post-dose up to a maximum of 8 cycles (6 months) ] [ Designated as safety issue: No ]
    Mean of individual observed Cmax values measured as micrograms per milliliter (mcg/mL).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours post-dose up to a maximum of 8 cycles (6 months) ] [ Designated as safety issue: No ]
    Area under the serum concentration time-curve from time zero to the last measured concentration. AUClast was estimated using non-compartmental methods on the sequence of sample measurements. Mean of individual observed AUClast values measured as nanograms multiplied by micrograms per milliliter (ng*mcg/mL).

  • Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Schedule A and Schedule B: Baseline and Day 21 of every even numbered cycle up to a maximum of 8 cycles (6 months) ] [ Designated as safety issue: No ]
    Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as the disappearance of all target and nontarget lesions. PR was defined as a ≥30% decrease in the sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD.

  • Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction.

  • Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction.

  • Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Assess activity of B cells (involved in production of antibodies) in presence of CP-870893. Clusters of differentiation (CD) are specific types of proteins on cell surface. CD19 is a B cell antigen receptor and is used to quantitate changes in proportion of B cells in peripheral blood as a consequence of therapy. Higher numbers may indicate a greater presence of CD19 on cell surface with increased potential for antigen response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.

  • Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Assess activity of B cells in the presence of CP-870893. CD40 is a costimulatory protein and is a target for CP-870893. Measurement of CD40 on white blood cells provides a measure of target modulation by CP-870893. Higher numbers may indicate potential for increased activation of antigen presenting cells. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.

  • Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Assess activity of B cells in the presence of CP-870893. CD23 is a low-affinity receptor that has a role in transportation in antibody feedback regulation. Agents that engage CD40 have been reported to increase CD23 expression; increased CD23 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate a potential for increased antibody response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.

  • Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Assess activity of B cells in presence of CP-870893. CD54 is an intercellular adhesion molecule. When activated, leukocytes bind to endothelial cells via CD54 and then transmigrate into tissues. Agents that engage CD40 have been reported to increase CD54 expression; increased CD54 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.

  • Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Assess activity of B cells in presence of CP-870893. CD86 is a protein expressed on antigen-presenting cells and provides co-stimulatory signals for T cell (role in cell-modulated immunity) activation. Agents that engage CD40 have been reported to increase CD86 expression; increased CD86 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.

  • Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax [ Time Frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose ] [ Designated as safety issue: No ]
    Assess activity of B cells in presence of CP-870893. HLA-DR is a component of the Major Histocompatibility Complex in humans and presents antigens for recognition by the immune system. Agents that engage CD40 have been reported to increase HLA-DR expression; increased HLA-DR expression may serve as a marker for CD40 binding by CP-870893. Positive values may indicate greater presence of cells associated with potential for antibody production. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.

  • Total and Neutralizing Human Antihuman Antibody (HAHA) Titer [ Time Frame: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose up to a maximum of 8 cycles (6 months) ] [ Designated as safety issue: Yes ]
    HAHA assessed as an indicator of immunogenicity to CP-870893.


Enrollment: 34
Study Start Date: November 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Schedule A
Schedule A (CP-870,893 administration schedule)
Drug: Paclitaxel + Carboplatin + CP-870,893
Paclitaxel is administered intravenously on day 1 of a 21-day cycle at a dose of 175 mg/m^2. Carboplatin is administered intravenously on day 1 of a 21-day cycle at AUC 6. CP-870,893 is administered intravenously on DAY 3 of a 21-day cycle in escalating doses (0.1 mg/kg and 0.2 mg/kg)
Schedule B
Schedule B (CP-870,893 administration schedule)
Drug: Paclitaxel + Carboplatin + CP-870,893
Paclitaxel is administered intravenously on day 1 of a 21-day cycle at a dose of 175 mg/m^2. Carboplatin is administered intravenously on day 1 of a 21-day cycle at AUC 6. CP-870,893 is administered intravenously on DAY 8 of a 21-day cycle in escalating doses (0.1 mg/kg and 0.2 mg/kg)

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with metastatic solid tumors, for whom carboplatin and paclitaxel are appropriate;
  • Patients >18 years of age;
  • Good performance status;
  • Adequate bone marrow and organ function

Exclusion Criteria:

  • Previous treatment with any other compound that targets CD40
  • Current or planned concurrent treatment with any anticancer agent;
  • Patients who have received bone marrow transplant;
  • History of autoimmune disorder
  • History (within the previous year) of heart failure or heart attack
  • Cancer-associated coagulation disorders
  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: NCT00607048

Locations
United States, California
Pfizer Investigational Site
Los Angeles, California, United States, 90025
Pfizer Investigational Site
Santa Monica, California, United States, 90404
United States, Pennsylvania
Pfizer Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Pfizer Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00607048     History of Changes
Other Study ID Numbers: A5021004
Study First Received: January 22, 2008
Results First Received: May 3, 2012
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Carboplatin
Paclitaxel
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2014