A Study Evaluating The PF-03084014 In Combination With Docetaxel In Patients With Advanced Breast Cancer

Breast Cancer Metastatic Clinical Trial

Official title:

Phase 1b Study Of Docetaxel + Pf 03084014 In Metastatic Or Locally Recurrent/Advanced Triple Negative Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01876251
• Other study ID #: A8641016
• Secondary ID: 2013-000659-41
• Status: Terminated
• Phase: Phase 1
• Start date: November 4, 2013
• Est. completion date: December 24, 2015

Study information

• Verified date: March 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is aimed to determine the tolerability of the PF-03084014 plus docetaxel combination in patients with advanced breast cancer. Preliminary information about the efficacy of the combination will also be collected.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 24, 2015
• Est. primary completion date: December 24, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease.

Exclusion Criteria:

• Prior treatment with a gamma secretase inhibitors or other Notch signaling inhibitors.

Related Conditions & MeSH terms

• Breast Cancer Metastatic
• Breast Neoplasms

Intervention

Drug:
• PF-03084014
Tablet, 10 mg, twice a day
• PF-03084014
Tablet, 50 mg, twice a day
• PF-03084014
Tablet, 100 mg, twice a day
• Docetaxel
Solution for IV infusion 75 mg/m^2, every 3 weeks
• Docetaxel
Solution for IV infusion 100 mg/m^2, every 3 weeks

Locations

Country	Name	City	State
Belgium	Jules Bordet Institut	Bruxelles
Belgium	Grand Hopital de Charleroi	Charleroi
Italy	Instituto Europeo di Oncologia	Milano
Spain	Instituto Catalan de Oncologia de L'Hospitalet de Llobregat(ICO)	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham, IDS Pharmacy	Birmingham	Alabama
United States	UNC Cancer Hospital Infusion Pharmacy	Chapel Hill	North Carolina
United States	UNC Hospitals, The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Karmanos Cancer Institute (KCI)	Detroit	Michigan
United States	Stanford Cancer Institute	Stanford	California
United States	Stanford Hospital & Clinics	Stanford	California
United States	Stanford Hospital & Clinics-DRUG SHIPMENT ADDRESS only	Stanford	California
United States	Stanford Women's Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1	Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia (Grade more than or equal to [>=] 3 and body temperature >=38.5 degrees Celsius); Grade >=3 neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade >=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities.	Cycle 1 Days 1-21
Primary	Progression-free Survival (PFS) at 6 Months - Expansion Cohort	The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Baseline till 6 months post-dose
Secondary	Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs (TEAEs) are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Causality assessment was made by the investigator. Grading was per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death related to AE.	Baseline up to 28-35 days after treatment discontinuation (up to Day 280)
Secondary	Number of Participants With Laboratory Abnormalities	Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick).	Baseline up to 28-35 days after treatment discontinuation (up to Day 280)
Secondary	Percentage of Participants With Objective Response (OR)	OR was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 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 less than [<] 10 millimeters [mm]). No new lesions. PR was defined as more than or equal to (>=) 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.	Baseline, every 6 weeks from Cycle 2 onwards up to 26 months
Secondary	Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort	Serum PF-03084014 pharmacokinetic (PK) parameters were calculated following twice daily (BID) doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1).	Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12)
Secondary	AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort	Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort	Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Cmax of Docetaxel in Dose-finding Cohort	Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort	Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Tmax of Docetaxel in Dose-finding Cohort	Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort	Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort	Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort	Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)	C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
Secondary	AUClast of PF-03084014 in the Expansion Cohort		C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Cmax of PF-03084014 in the Expansion Cohort		C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Tmax of PF-03084014 in the Expansion Cohort		C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Ctrough of PF-03084014 in the Expansion Cohort		C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
Secondary	Duration of Response (DR)	Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.	Baseline up to 28-35 days after treatment discontinuation (up to Day 280)
Secondary	Number of Participants With QTc Values Meeting Categorical Summarization Criteria	Criteria for categorical summarization of the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT) corrected for heart rate (QTc) using Bazett's correction (QTcB) or Fridericia's correction (QTcF) included: maximum QTcB or QTcF less than or equal to (<=) 450 milliseconds (msec), 450 to <=480 msec, 480 to <=500 msec, more than (>) 500 msec; maximum QTcB or QTcF changes (increases/decreases) from baseline (BL) less than (<) 30 msec, 30 to <60 msec, more than or equal to (>=) 60 msec.	Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12)
Secondary	Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood	As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4.	C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12)

External Links

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