Clinical trial NCT03042910: A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors
Official title: A PHASE 1, OPEN-LABEL STUDY TO ASSESS THE EFFECTS OF TALAZOPARIB ON CARDIAC REPOLARIZATION IN PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2017-02-03
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the effects of talazoparib on cardiac repolarization in patients with advanced solid tumors with no available standard treatment options.

Detailed description: For further talazoparib treatment, patients must enroll and initiate continued talazoparib treatment in a separate open label extension study within 30 days after the last dose of study drug.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age and willing and able to provide informed consent.
2. Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the investigator.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
4. Estimated life expectancy of ≥ 3 months.
5. Able to swallow the study drug, have no known intolerance to the study drug or excipients, and comply with study requirements.
6. Female patients of childbearing potential must have a negative pregnancy test at screening and must agree to use a highly effective birth control method from the time of the first dose of study drug through 45 days after last dose of study drug.
7. Male patients must use a condom when having sex with a pregnant woman or with a woman of childbearing potential from the time of the first dose of study drug through 105 days after last dose of study drug. Contraception should be considered for a nonpregnant female partner of childbearing potential.
8. Male and female patients must agree not to donate sperm or eggs, respectively, from the first dose of study drug through 105 days and 45 days after the last dose of study drug, respectively.
9. Female patients may not be breastfeeding at screening and must not breastfeed during study participation through 45 days after the last dose of study drug.

Exclusion Criteria:

1. Use of antineoplastic therapies within 21 days before day 1.
2. Use of any other investigational agent within 21 days before day 1.
3. Have not recovered (recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] grade ≤ 1) from the acute toxicities of previous therapy, except treatment related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
4. Electrolyte abnormality that has not responded to correction, including hypokalemia or hypocalcemia less than the lower limit of normal, or hyperkalemia or hypercalcemia greater than the upper limit of normal (ULN).
5. Major surgery within 14 days before day 1.
6. Diagnosis of myelodysplastic syndrome (MDS) or a hematologic malignancy.
7. Clinically significant cardiovascular disease.
8. Significant organ dysfunction.
9. Gastrointestinal disorder affecting absorption.
10. Current or anticipated use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP.
11. Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the investigator or medical monitor.

Primary outcomes:
measure: Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
timeFrame: Baseline (Day -1) to Day 22
measure: Concentration Slope of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22
timeFrame: Baseline (Day -1) to Day 22
Secondary outcomes:
measure: Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Time-matched Mean Change From Baseline in Heart Rate
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Time-matched Mean Change From Baseline in PR Interval
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Time-matched Mean Change From Baseline in QRS Interval
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Time-matched Mean Change From Baseline in QT Interval
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Time-matched Mean Change From Baseline in RR Interval
timeFrame: Baseline (Day -1 time matched for each time point); 1, 2, 4 and 6 hours post-dose on Day 1; pre-dose on Day 2; pre-dose, 1, 2, 4 and 6 hours post-dose on Day 22
measure: Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology
timeFrame: Baseline to Day 22
measure: Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria
timeFrame: Baseline (mean of all ECGs on Day -1 and pre-dose on Day 1) to Day 22
measure: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths
timeFrame: Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)
measure: Number of Participants With Clinically Notable Changes in Vital Signs Measurements
timeFrame: Screening (Day -29 to Day -2) to follow-up (30 days post last dose on Day 22)
measure: Number of Participants With Clinically Significant Laboratory Test Abnormalities
timeFrame: Baseline to follow-up (30 days post last dose on Day 22, i.e. up to Day 52)
measure: Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours After Dosing (AUC24) of Plasma Talazoparib on Day 1 and Day 22
timeFrame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
measure: Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22
timeFrame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
measure: Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22
timeFrame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Day 1; pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
measure: Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22
timeFrame: Pre-dose, Day 22
measure: Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22
timeFrame: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
measure: Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22
timeFrame: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
state: California
city: Burbank
country: United States
facility: UCLA Hematology/Oncology - Burbank
state: California
city: Fullerton
country: United States
facility: St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
state: California
city: Los Angeles
country: United States
facility: UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: TRIO-US Central Administration
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Los Angeles
country: United States
facility: UCLA West Medical Pharmacy. Attn: Steven L. Wong, Pharm.D.
state: California
city: Pasadena
country: United States
facility: UCLA Hematology/Oncology - Pasadena
state: California
city: Porter Ranch
country: United States
facility: UCLA Hematology/Oncology - Porter Ranch
state: California
city: Redondo Beach
country: United States
facility: Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Valencia
country: United States
facility: UCLA Hematology/Oncology - Santa Clarita
state: California
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Hospital West
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: