Dose Finding Study Of CP-870,893, An Immune System Stimulating Antibody, In Combination With Paclitaxel And Carboplatin For Patients With Metastatic Solid Tumors
- Registration Number
- NCT00607048
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a dose-finding study; therefore, there is no hypothesis testing
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Schedule A Paclitaxel + Carboplatin + CP-870,893 Schedule A (CP-870,893 administration schedule) Schedule B Paclitaxel + Carboplatin + CP-870,893 Schedule B (CP-870,893 administration schedule)
- Primary Outcome Measures
Name Time Method Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) Schedule (Sch) A Cycle 1 / Day 3 or Schedule B Cycle 1 / Day 8 up to Cycle 1 / Day 21 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
Name Time Method Maximum Observed Serum Concentration (Cmax) 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) 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) 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) 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) Schedule A and Schedule B: Baseline and Day 21 of every even numbered cycle up to a maximum of 8 cycles (6 months) 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) 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 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 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 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) Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose 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 Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose 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 Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose 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 Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose 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 Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose 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 Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose 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 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) HAHA assessed as an indicator of immunogenicity to CP-870893.
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇺🇸San Antonio, Texas, United States