- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00607048
Dose Finding Study Of CP-870,893, An Immune System Stimulating Antibody, In Combination With Paclitaxel And Carboplatin For Patients With Metastatic Solid Tumors
February 22, 2017 updated by: Hoffmann-La Roche
A Phase 1 Study Of CP- 870,893 In Combination With Paclitaxel And Carboplatin In Patients With Metastatic Solid Tumors
This is a dose-finding study; therefore, there is no hypothesis testing
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
34
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90025
- Pfizer Investigational Site
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Santa Monica, California, United States, 90404
- Pfizer Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Pfizer Investigational Site
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Texas
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San Antonio, Texas, United States, 78229
- Pfizer Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Schedule A
Schedule A (CP-870,893 administration schedule)
|
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)
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)
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Other: Schedule B
Schedule B (CP-870,893 administration schedule)
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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)
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)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Schedule (Sch) A Cycle 1 / Day 3 or Schedule B Cycle 1 / Day 8 up to Cycle 1 / Day 21
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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Mean of individual observed Cmax values measured as micrograms per milliliter (mcg/mL).
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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)
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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)
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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).
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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)
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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)
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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.
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Schedule A and Schedule B: Baseline and Day 21 of every even numbered cycle up to a maximum of 8 cycles (6 months)
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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
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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.
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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
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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
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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.
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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
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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
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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.
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Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
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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
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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.
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Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
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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
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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.
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Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
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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
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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.
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Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
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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
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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.
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Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
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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
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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.
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Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
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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)
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HAHA assessed as an indicator of immunogenicity to CP-870893.
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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)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2007
Primary Completion (Actual)
July 1, 2009
Study Completion (Actual)
July 1, 2009
Study Registration Dates
First Submitted
January 22, 2008
First Submitted That Met QC Criteria
January 22, 2008
First Posted (Estimate)
February 5, 2008
Study Record Updates
Last Update Posted (Actual)
March 27, 2017
Last Update Submitted That Met QC Criteria
February 22, 2017
Last Verified
February 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- A5021004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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