A Study Of PF-06664178 In Patients With Advanced Solid Tumors

Neoplasms Clinical Trial

Official title:

A Phase 1, Dose Escalation Study Of Pf-06664178 In Patients With Locally Advanced Or Metastatic Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02122146
• Other study ID #: B7401001
• Secondary ID: 2015-002704-84
• Status: Terminated
• Phase: Phase 1
• First received: April 17, 2014
• Last updated: August 9, 2017
• Start date: August 2014
• Est. completion date: June 2016

Study information

• Verified date: August 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• PF-06664178
Part 1 - PF-06664178 will be administered intravenously every 21 days in cohorts of 2 or more patients starting at a dose of 0.15 mg/kg. Increases in dose will continue until MTD is determined.
• PF-06664178
Part 2 - patients with select tumor types (Non Small Cell Lung Cancer ovarian cancer, and breast cancer ) will be treated at the MTD selected in Part 1.

Locations

Country	Name	City	State
United States	Anschutz Cancer Pavilion	Aurora	Colorado
United States	University of Colorado Denver CTO (CTRC)	Aurora	Colorado
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	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD)	Number of participants that experienced dose limiting toxicities(DLTs) at given dose level.	Day 1 up to Day 21
Primary	Number of Patients With All-Causality Treatment-Emergent Adverse Events(TEAEs) [Part 2 & 3]	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.	Day 1 up to Day 21
Primary	Number of Participants With Laboratory Abnormalities [Part 2 & 3]	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.	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)
Secondary	Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs ) [Part 1]	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.	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)
Secondary	Number of Participants With Laboratory Abnormalities[Part 1]	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.	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)
Secondary	Overall Incidence of Anti-PF-06664178-Antibodies[Part 1]	Number of participants with the presence of anti-PF-06664178 antibodies	Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment
Secondary	Overall Incidence of Anti-PF-06664178-Antibodies [Part 2 & 3]	Number of participants with the presence of anti-PF-06664178 antibodies	Day 1, 15, 21, and every 21 days thereafter up to 24 months, and end of treatment
Secondary	Overall Number of Participants With Objective Tumor Response[Part 1]	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.	Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Secondary	Overall Number of Participants With Objective Tumor Response [Part 2 & 3]	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)	Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Secondary	Maximum Observed Plasma Concentration (Cmax) for PF-06664178 [Part 1 ,2 & 3]	Cmax of PF-06664178 was observed directly from data	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
Secondary	Maximum Observed Plasma Concentration (Cmax) for Total Antibody (PF-06479118) [Part 1 ,2 & 3]	Cmax of total antibody PF-06479118 was observed directly from data	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
Secondary	Maximum Observed Plasma Concentration (Cmax) for Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]	Cmax of unconjugated payload PF-06380101 was observed directly from data	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
Secondary	Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of PF-06664178 [Part 1 ,2 & 3]	AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval	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
Secondary	Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Total Antibody(PF-06479118) [Part 1 ,2 & 3]	AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval.	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
Secondary	Area Under the Concentration-Time Curve Over the Dosing Interval(AUCtau) of Unconjugated Payload(PF-06380101) [Part 1 ,2 & 3]	AUCtau refers to area under the concentration-time profile from time zero to the time tau, the dosing interval.	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
Secondary	Systemic Clearance (CL) of PF-06664178 [Part 1 ,2 & 3]	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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
Secondary	Systemic Clearance (CL) of Total Antibody (PF-06479118) [Part 1 ,2 & 3]	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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
Secondary	Systemic Clearance (CL) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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
Secondary	Volume of Distribution (Vss) of PF-06664178 [Part 1 ,2 & 3]	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.	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
Secondary	Volume of Distribution (Vss) of Total Antibody (PF-06479118) [Part 1 ,2 & 3]	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.	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
Secondary	Volume of Distribution (Vss) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]	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.	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
Secondary	Terminal Elimination Half-Life (t1/2) of PF-06664178 [Part 1 ,2 & 3]	Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half	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
Secondary	Terminal Elimination Half-Life (t1/2) of Total Antibody (PF-06479118)[Part 1 ,2 & 3]	Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half	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
Secondary	Terminal Elimination Half-Life (t1/2) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]	Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half	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
Secondary	Trop-2 Expression Levels on Archived Tissue [Part 2 & 3]	Number of participents meeting the following criterion for Trop-2 expression assessment : low expression, medium expression and high expression	Day 1
Secondary	Accumulation Ratio (Rac) of PF-06664178 [Part 1 ,2 & 3]	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.	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
Secondary	Accumulation Ratio (Rac) of Total Antibody (PF-06479118) [Part 1 ,2 & 3]	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.	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
Secondary	Accumulation Ratio (Rac) of Unconjugated Payload (PF-06380101) [Part 1 ,2 & 3]	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.	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

External Links

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