PF-06671008 Dose Escalation Study in Advanced Solid Tumors
- Registration Number
- NCT02659631
- Lead Sponsor
- Pfizer
- Brief Summary
The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06671008 in patients with advanced solid tumors with the potential to have P-cadherin expression. The study will then expand to look at the selected dose in patients with P-cadherin expressing TNBC, CRC or NSCLC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PF-06671008 PF-06671008 -
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1 Baseline through Day 21 (Cycle 1) DLT was defined as any of the following adverse events occurring in the first cycle of treatment (21 days after the first dose): a) Hematologic: Febrile neutropenia defined as an absolute neutrophil count (ANC) \<1.0 x 10\^9/L with a single temperature of \>38.3°C, or 101°F, or a sustained temperature of \>=38°C, or 100.4°F, for more than one hour; b) Non-hematologic: Delay by more than 2 weeks in receiving the next scheduled dose due to persisting treatment related toxicities; c) Any grade 3 or 4 clinically-relevant hematologic or non-hematologic toxicity.
Number of Participants With Objective Response (OR) - Part 2 Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months Number of participants with OR based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1.
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions.
PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
- Secondary Outcome Measures
Name Time Method Maximum Serum Concentration (Cmax) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose Maximum serum concentration (Cmax) of PF-06671008 was observed directly from data.
Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose Tau refers to the dosing interval, which was 1 week. Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method.
Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.Number of Participants With Progression Free Survival (PFS) - Part 2 Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months The period from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence.
Number of Participants With OR - Part 1 Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months Number of participants with OR based on assessment of CR or PR according to RECIST v1.1.
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions.
PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.Terminal Elimination Half-life (t1/2) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose Terminal elimination half-life (t1/2) of PF-06671008 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Arithmetic mean was not calculated if fewer than 3 participants had reportable parameter values.Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose AUCinf was calculated as AUClast +(Clast\*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.Systemic Clearance (CL) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose Systemic Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms.
Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.Apparent Clearance (CL/F) of PF-06671008 C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose Apparent Clearance (CL/F) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arm.
Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.Number of Participants With Overall Survival (OS) - Part 2 Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months The period from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008 C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months ADA against PF-06671008 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer \>=1.18 was considered positive.
Trial Locations
- Locations (9)
Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center- Clinical Trials Office
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center - Westchester
🇺🇸Harrison, New York, United States
The University of Texas - M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States