A Study Of PF-06664178 In Patients With Advanced Solid Tumors
- Registration Number
- NCT02122146
- Lead Sponsor
- Pfizer
- Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-06664178 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
- 31
- Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
- Performance Status of 0 or 1
- Adequate bone marrow, kidney and liver function
- Part 2 includes target expressing NSCLC, ovarian or breast cancer patients
- Brain metastases requiring steroids
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
- Active and clinically significant bacterial, fungal, or viral infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description PF-06664178 PF-06664178 Experimental
- Primary Outcome Measures
Name Time Method First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) Day 1 up to Day 21 Number of participants that experienced dose limiting toxicities(DLTs) at given dose level.
Number of Patients With All-Causality Treatment-Emergent Adverse Events(TEAEs) [Part 2 & 3] Day 1 up to Day 21 An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.
Number of Participants With Laboratory Abnormalities [Part 2 & 3] On Day1, Day4, Day8, Day15 of the first cycle; on Day1, Day8, Day15 of the second cycle; on Day 1 of the subsequent cycles; end of treatment visit(no longer than 1 week after the patient has been discontinued) Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology( hemoglobin, platelets, white blood cell count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils), chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate), coagulation (prothrombin time or International normalized ratio, partial thromboplastin time), Urinalysis (urine protein, urine blood) and pregnancy test.
- Secondary Outcome Measures
Name Time Method Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1] From screening up to 28 days after the last treatment administration in each cycle, and follow-up visits(At least 28 days and no more than 35 days after discontinuation of treatment) An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.
Number of Participants With Laboratory Abnormalities[Part 1] Screening; on Day1, Day4, Day8, Day15 of the first cycle; on Day1, Day8, Day15 of the second cycle; on Day 1 of the subsequent cycles; end of treatment visit(no longer than 1 week after the patient has been discontinued) Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology( hemoglobin, platelets, white blood cell count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils), chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate), coagulation (prothrombin time or International normalized ratio, partial thromboplastin time), Urinalysis (urine protein, urine blood) and pregnancy test.
Overall Incidence of Anti-PF-06664178-Antibodies[Part 1] Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment Number of participants with the presence of anti-PF-06664178 antibodies
Overall Number of Participants With Objective Tumor Response [Part 2 & 3] Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 by calculating the Overall Response Rate (ORR), and Prolonged Stable Disease (SD).No Progression Free Survival (PFS) was completed. The criterion is as follow: Objective Progression(PD), Stable (SD), symptomatic deterioration(Sym), and Indeterminate (In)
Maximum Observed Plasma Concentration (Cmax) for Total Antibody (PF-06479118) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Cmax of total antibody PF-06479118 was observed directly from data
Overall Incidence of Anti-PF-06664178-Antibodies [Part 2 & 3] Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment Number of participants with the presence of anti-PF-06664178 antibodies
Maximum Observed Plasma Concentration (Cmax) for Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Cmax of unconjugated payload PF-06380101 was observed directly from data
Overall Number of Participants With Objective Tumor Response[Part 1] Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months Objective tumor response, was assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 by calculating the Overall Response Rate, and Prolonged Stable Disease. The criterion is defined as: Objective Progression(PD):20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5mm; Stable (SD): All target lesions must be assessed. Stable can follow PR only in the rare case that the sum increases by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds; symptomatic deterioration(Sym):Participants with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time; Indeterminate (In):Progression has not been determined and one, or more non-target sites were not assessed, or assessment methods were inconsistent with those used at baseline.
Maximum Observed Plasma Concentration (Cmax) for PF-06664178 [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Cmax of PF-06664178 was observed directly from data
Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of PF-06664178 [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval
Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Total Antibody(PF-06479118) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval.
Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Unconjugated Payload(PF-06380101) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval.
Systemic Clearance (CL) of PF-06664178 [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Systemic Clearance (CL) of Total Antibody (PF-06479118) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Systemic Clearance (CL) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Volume of Distribution (Vss) of PF-06664178 [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Volume of Distribution (Vss) of Total Antibody (PF-06479118) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Volume of Distribution (Vss) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Terminal Elimination Half-Life (t1/2) of PF-06664178 [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half
Terminal Elimination Half-Life (t1/2) of Total Antibody (PF-06479118)[Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half
Terminal Elimination Half-Life (t1/2) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half
Trop-2 Expression Levels on Archived Tissue [Part 2 & 3] Day 1 Number of participents meeting the following criterion for Trop-2 expression assessment : low expression, medium expression and high expression
Accumulation Ratio (Rac) of PF-06664178 [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval.
Accumulation Ratio (Rac) of Total Antibody (PF-06479118) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval.
Accumulation Ratio (Rac) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3] 0, 1, 4, 24 hours post-dose on Day 1, and on Day 4, Day 8 and Day 15 of cycles 1 and 4; 0, 1hour post-dose on Cycle 2, 3 and every cycle after cycle 4, end of treatment Accumulation ratio refers to AUCtau for cycle 4/AUCtau for cycle 1, where AUCtau is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to the time tau, the dosing interval.
Trial Locations
- Locations (10)
Swedish Medical Center
🇺🇸Seattle, Washington, United States
USC/Norris Comprehensive Cancer Center / Investigational Drug Services
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of Colorado Denver CTO (CTRC)
🇺🇸Aurora, Colorado, United States
Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
LAC&USC Medical Center
🇺🇸Los Angeles, California, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States