A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors

NCT03042910 | Completed Phase 1 Results

• 2 other identifiers: MDV3800-14C3441005
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 19

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF)

  QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.

  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

• Intercept of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22

  A linear mixed effects modeling approach was used to examine the relationship between the change from baseline in QTcF and the plasma concentration of talazoparib. The model included plasma concentration, time (categorical), and treatment with random participant effects on plasma concentration and the intercept. Equation used for modeling was: Y\_lkt= μ\_l+ p\_t+ θ × C\_lkt + W\_k + D\_k × C\_kt + ε\_lkt, where the dependent variable Y\_lkt was for the l (treatment), k (participants) and t (time point). Parameter were: μ\_l was the treatment specific intercept, θ was the slope, C was the concentration, W\_k was the random patient effect on the intercept, D\_k was the random patient effect on the slope, p\_t was the time effect on the intercept and ε\_lkt was the residual error.

  Baseline (Day -1) to Day 22

• Concentration Slope of Predicted Linear Mixed Effects Models for Change From Baseline in QTcF Versus Plasma Talazoparib Concentrations at Day 22

  A linear mixed effects modeling approach was used to examine the relationship between the change from baseline in QTcF and the plasma concentration of talazoparib. The model included plasma concentration, time (categorical), and treatment with random participant effects on plasma concentration and the intercept. Equation used for modeling was: Y\_lkt= μ\_l+ p\_t+ θ × C\_lkt+ W\_k+ D\_k × C\_kt+ ε\_lkt, where the dependent variable Y\_lkt was for the l (treatment), k (participants) and t (time point). Parameter were: μ\_l was the treatment specific intercept, θ was the slope, C was the concentration, W\_k was the random patient effect on the intercept, D\_k was the random patient effect on the slope, p\_t was the time effect on the intercept and ε\_lkt was the residual error.

  Baseline (Day -1) to Day 22

Secondary Outcomes (17)

• Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Bazett's Correction Fomulation (QTcB)

  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

• Time-matched Mean Change From Baseline in Heart Rate

  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

• Time-matched Mean Change From Baseline in PR Interval

  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

• Time-matched Mean Change From Baseline in QRS Interval

  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

• Time-matched Mean Change From Baseline in QT Interval

  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

Study Arms (1)

Patients with advanced solid tumors

EXPERIMENTAL

Talazoparib 1 mg daily

Drug: Talazoparib

Interventions

Talazoparib DRUG

Talazoparib 1 mg orally once daily.

Also known as: MDV3800, BMN673

Patients with advanced solid tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age and willing and able to provide informed consent.
• Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Estimated life expectancy of ≥ 3 months.
• Able to swallow the study drug, have no known intolerance to the study drug or excipients, and comply with study requirements.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Use of antineoplastic therapies within 21 days before day 1.
• Use of any other investigational agent within 21 days before day 1.
• 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.
• 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).
• Major surgery within 14 days before day 1.
• Diagnosis of myelodysplastic syndrome (MDS) or a hematologic malignancy.
• Clinically significant cardiovascular disease.
• Significant organ dysfunction.
• Gastrointestinal disorder affecting absorption.
• Current or anticipated use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP.
• 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.

Sponsors & Collaborators

• Pfizer: lead
• Medivation, Inc.: collaborator

Study Sites (19)

CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

UCLA Hematology/Oncology - Burbank

Burbank, California, 91505, United States

Location

St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.

Los Angeles, California, 90095-7349, United States

Location

Ronald Reagan UCLA Medical Center, Drug Information Center

Los Angeles, California, 90095, United States

Location

TRIO-US Central Administration

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

UCLA West Medical Pharmacy. Attn: Steven L. Wong, Pharm.D.

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology - Pasadena

Pasadena, California, 91105, United States

Location

UCLA Hematology/Oncology - Porter Ranch

Porter Ranch, California, 91326, United States

Location

Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

UCLA Hematology/Oncology - Santa Clarita

Valencia, California, 91355, United States

Location

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

Orlando Health, Inc.

Orlando, Florida, 32806, United States

Location

Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46804, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46845, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

talazoparib

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: February 3, 2017
• Study Start: October 13, 2016
• Primary Completion: May 30, 2017
• Study Completion: June 22, 2017
• Last Updated: December 17, 2019
• Results First Posted: December 17, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)