A Study Of PF-06263507 In Patients With Advanced Solid Tumors
- Conditions
- Carcinoma, Non Small Cell LungOvarian NeoplasmsNeoplasmsBreast Neoplasms
- Interventions
- Registration Number
- NCT01891669
- Lead Sponsor
- Pfizer
- Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-06263507 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 26
- Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for which no standard therapy is available.
- Performance Status of 0 or 1.
- Adequate bone marrow, kidney, liver, and heart function.
- Brain metastases requiring steroids.
- Major surgery or anti-cancer therapy within 4 weeks of study treatment start.
- Active bacterial, fungal or viral infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Part 1 PF-06263507 -
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-limiting Toxicities (DLT) Baseline up to Cycle 2 Day 1 (22 days) DLT was defined as any of the following adverse events (AEs) occurring in the first cycle of treatment (21 days) which were attributable to PF-06263507: 1) Grade 4 neutropenia lasting \>7 days, 2) Febrile neutropenia, 3) Grade \>=3 neutropenia with infection, 4) Any grade thrombocytopenia associated with clinically significant or life-threatening bleeding, 4) Grade 4 thrombocytopenia, 5) Any grade \>=3 non-hematologic toxicities, 6) A positive cardiac troponin I result, 7) Persisting non-hematologic toxicities resulted in more than 2 weeks delay in receiving the next scheduled cycle. Severity of AEs was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (TEAEs), by Maximum National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade Baseline, Day 1 to 15 for Cycle 1, Day 1 to end of treatment for Cycle 2 and subsequent cycles, and follow-up. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade was reported.
Number of Participants With Treatment-related AEs, by Maximum NCI CTCAE (Version 4.0) Grade Baseline, Day 1 to 15 for Cycle 1, Day 1 to end of treatment for Cycle 2 and subsequent cycles, and follow-up. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade was reported.
Number of Participants With Hematological Test Abnormalities in All Cycles. Baseline, Days 1, 3, 8 and 15 for Cycle 1, Days 1, 8, 15 for Cycle 2 and subsequent cycles, and end of treatment Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 hematological test abnormalities.
Number of Participants With Chemistry Test Abnormalities in All Cycles. Baseline, Days 1, 3, 8 and 15 for Cycle 1, Days 1, 8, 15 for Cycle 2 and subsequent cycles, and end of treatment Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 chemistry tests abnormalities.
Number of Participants With Abnormalities in Urine Protein in All Cycles. Baseline, Day 15 for Cycle 1, Day 1 for Cycle 2 and subsequent cycles, and end of treatment Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 abnormalities in urine protein.
Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria Baseline, Days 1, 3, 8 and 15 for Cycle 1, Days 1, 8, 15 for Cycle 2 and subsequent cycles, end of treatment, and follow-up. Criteria for potentially clinically important (PCI) change in vital signs included: sitting systolic blood pressure (SBP) of \<90 millimeters of mercury (mm Hg) or change in sitting SBP of \>=30 mm Hg, sitting diastolic blood pressure (DBP) of \<50 mm Hg or change in sitting DBP of \>=20 mm Hg, sitting pulse rate of \<40 or \>120 beats per minute (bpm).
Number of Participants With Positive Anti-PF-06263507 Antibody Pre-dose Day 1, Cycle 1 Day 15, Day 1 of every Cycle, up to 21 days after the last dose of study medication The number of participants with positive anti-PF-06263507 antibody.
Number of Participants With Best Overall Response (BOR) Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months. Number of participants with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)\>=30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD) \>=20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of \>=1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Objective Response Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months. Number of particpants with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.
Overall Survival Baseline to death Overall survival was defined as the time from initial dose until death from any cause, and was measured in the intent-to-treat population.
Time to Reach Maximum Observed Serum PF-06263507 Concentration (Tmax) Baseline,Cycle 1 Day 1 pre-dose,1,4,8,12,24, and 48 hrs post dose,Day 5,Day 8 and Day 15;Day 1 of Cycle 2 and 3,Day 1 of Cycle 4 pre-dose,1,8,12,24 hr post dose, Day 8 and Day 15,every cycle thereafter on day 1 pre-dose, and up to 21 days after last dose. Time to Reach Maximum Observed Serum PF-06281192 Concentration (Tmax) Baseline,Cycle 1 Day 1 pre-dose,1,4,8,12,24, and 48 hrs post dose,Day 5,Day 8 and Day 15;Day 1 of Cycle 2 and 3,Day 1 of Cycle 4 pre-dose,1,8,12,24 hr post dose, Day 8 and Day 15,every cycle thereafter on day 1 pre-dose, and up to 21 days after last dose. Time to Reach Maximum Observed Serum PF-06264490 Concentration (Tmax) Baseline,Cycle 1 Day 1 pre-dose,1,4,8,12,24, and 48 hrs post dose,Day 5,Day 8 and Day 15;Day 1 of Cycle 2 and 3,Day 1 of Cycle 4 pre-dose,1,8,12,24 hr post dose, Day 8 and Day 15,every cycle thereafter on day 1 pre-dose, and up to 21 days after last dose.
Trial Locations
- Locations (4)
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States