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Solid TumorPhase 1NCT03042910

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

A Phase 1 study testing Talazoparib in people with Solid Tumor, run by Pfizer at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Talazoparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
19 sitesUnited States
Study dates
13 Oct 2016to 22 Jun 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

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

    Bakersfield, California, 93309

  • UCLA Hematology/Oncology - Burbank

    Burbank, California, 91505

  • Fort Wayne Medical Oncology and Hematology, Inc.

    Fort Wayne, Indiana, 46804

  • Fort Wayne Medical Oncology and Hematology, Inc.

    Fort Wayne, Indiana, 46845

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

    Fullerton, California, 92835

  • Memorial Cancer Institute at Memorial Regional Hospital

    Hollywood, Florida, 33021

  • Memorial Regional Hospital

    Hollywood, Florida, 33021

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

    Los Angeles, California, 90095-7349

  • Ronald Reagan UCLA Medical Center, Drug Information Center

    Los Angeles, California, 90095

  • TRIO-US Central Administration

    Los Angeles, California, 90095

  • UCLA Hematology/Oncology

    Los Angeles, California, 90095

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

    Los Angeles, California, 90095

  • Orlando Health, Inc.

    Orlando, Florida, 32806

  • UCLA Hematology/Oncology - Pasadena

    Pasadena, California, 91105

  • Memorial Hospital West

    Pembroke Pines, Florida, 33028

  • UCLA Hematology/Oncology - Porter Ranch

    Porter Ranch, California, 91326

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

    Redondo Beach, California, 90277

  • UCLA Hematology/Oncology - Santa Monica

    Santa Monica, California, 90404

  • UCLA Hematology/Oncology - Santa Clarita

    Valencia, California, 91355

Other trials in United States

About this study

Official title: A PHASE 1, OPEN-LABEL STUDY TO ASSESS THE EFFECTS OF TALAZOPARIB ON CARDIAC REPOLARIZATION IN PATIENTS WITH ADVANCED SOLID TUMORS

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.

Read the 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.

Conditions
Solid Tumor
Being tested
Talazoparib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TalazoparibDrug

    Also called MDV3800, BMN673

    Talazoparib 1 mg orally once daily.

Study groups in NCT03042910
Study groupRoleWhat they receive
Patients with advanced solid tumorsExperimentalTalazoparib 1 mg daily
Receives: Drug: Talazoparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: Baseline (Day -1) to Day 22

  3. 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.

    Measured: Baseline (Day -1) to Day 22

Secondary outcomes (17)

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

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

    Measured: 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

  2. Time-matched Mean Change From Baseline in Heart Rate

    Measured: 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

  3. Time-matched Mean Change From Baseline in PR Interval

    PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.

    Measured: 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

  4. Time-matched Mean Change From Baseline in QRS Interval

    QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization.

    Measured: 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

  5. Time-matched Mean Change From Baseline in QT Interval

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

    Measured: 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

  6. Time-matched Mean Change From Baseline in RR Interval

    RR interval is the time elapsing between two consecutive R waves in the electrocardiogram.

    Measured: 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

  7. Number of Participants With Treatment-emergent Abnormalities in 12-lead Electrocardiogram (ECG) Morphpology

    Morphological analyses were performed with regard to the ECG waveform interpretation as defined by the central ECG laboratory's cardiologist. Numbers of participants with new onsets for the following variables were counted: atrial fibrillation or flutter, second-degree heart block, third degree heart block, complete right bundle branch block, complete left bundle branch block, ST segment depression, ST segment elevation, T-wave abnormalities (negative T waves only), myocardial infarction pattern, and any new abnormal U waves. "New" was defined as "not present on any baseline ECG but present on any on-treatment ECG". Number of participants with abnormality in any of the variables were reported.

    Measured: Baseline to Day 22

  8. Number of Participants With Clinically Significant Findings in 12-lead Electrocardiogram (ECG) Parameters Meeting Predefined Criteria

    Criteria for clinically significant: Maximum QTcF >450 msec, Maximum QTcF >480 msec, Maximum QTcF >500 msec, Maximum QTcB >450 msec, Maximum QTcB >480 msec, Maximum QTcB >500 msec, Maximum QT Interval >500 msec, Maximum QTcF Increase <=30 msec, Maximum QTcF Increase 30 to <=60 msec, Maximum QTcF Increase <=60 msec, Maximum PR interval increase >200 msec and >=25%, Maximum QRS interval increase >100 msec and >=25%, Maximum heart rate increase >100 bpm and >25% and Maximum heart rate decrease <50 bpm and >25%.

    Measured: Baseline (mean of all ECGs on Day -1 and pre-dose on Day 1) to Day 22

  9. Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, AEs of Special Interest, and Deaths

    An adverse event(AE)was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not related to the study drug. A serious adverse event(SAE)was an AE that resulted in: death; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect; was life-threatening (immediate risk of death); hospitalization or prolongation of existing hospitalization; or considered to be an important medical event. Treatment-emergent AEs (TEAEs) are AEs occurred on or after the administration of study drug. AEs related to study drug was any AE with at least a possible relationship to the study drug as assessed by the investigator. AEs of special interest were diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and abnormal liver test results that met predefined criteria.

    Measured: Day 1 to follow-up (30 days post last dose, i.e. up to 52 days)

  10. Number of Participants With Clinically Notable Changes in Vital Signs Measurements

    Clinically notable changes included: High systolic blood pressure (SBP):>=155 millimeters of mercury (mmHg) with increase >=30 mmHg, low SBP <=90 mmHg with decrease >=20 mmHg, Both high and low SBP (i.e high SBP >=155 mmHg with increase >=30 mmHg and low SBP <=90 mmHg with decrease >=20 mmHg), High diastolic blood pressure (DBP):>=100 mmHg with increase >=15 mmHg), Low DBP (<=50 mmHg with decrease >=15 mmHg), Both high and low DBP, Heart rate >=100 bpm with increase >=30 bpm, Heart rate <=50 bpm with decrease >=15 bpm, Respiratory rate >=25 bpm, Respiratory rate <10 bpm, Oral body temperature >39 degree and Oral body temperature <=35 degree.

    Measured: Screening (Day -29 to Day -2) to follow-up (30 days post last dose on Day 22)

  11. Number of Participants With Clinically Significant Laboratory Test Abnormalities

    Laboratory test included: hematology (hematocrit, hemoglobin, mean corpuscular volum, red blood cell count, platelet count, white blood cell count with differential [total neutrophils, eosinophils, monocytes, basophils, and lymphocytes]),chemistry (albumin, total protein, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, non-fasting glucose, carbon dioxide, calcium, chloride, magnesium, phosphate, potassium, sodium and lactate dehydrogenase), and additional tests (urine or serum pregnancy tests for women of childbearing potential). Clinically significant laboratory abnormality was determined by the investigator.

    Measured: Baseline to follow-up (30 days post last dose on Day 22, i.e. up to Day 52)

  12. 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

    Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.

    Measured: 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

  13. Maximum Plasma Concentration (Cmax) of Plasma Talazoparib on Day 1 and Day 22

    Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.

    Measured: 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

  14. Time for Cmax (Tmax) of Plasma Talazoparib on Day 1 and Day 22

    Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.

    Measured: 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

  15. Predose Concentration (Ctrough) of Plasma Talazoparib on Day 22

    Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.

    Measured: Pre-dose, Day 22

  16. Apparent Clearance After Oral Dose (CL/F) of Plasma Talazoparib on Day 22

    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed. Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.

    Measured: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22

  17. Accumulation Ratio (Rac) of Plasma Talazoparib on Day 22

    Rac was calculated as, area under the curve from time zero to end of dosing interval on Day 22 (AUCtau) divided by area under the curve from time zero to end of dosing interval on Day 1 (AUCtau). Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 6 hours. Day 22 subpopulation: amongst the participants with reported pharmacokinetic (PK) parameters on Day 22, exclusion of values from the summary statistics calculations due to dose modifications (eg, dose interruptions, dose reductions) was handled on a case by case basis, resulting in a subpopulation of participants with no prior dose modifications.

    Measured: Pre-dose, 1, 2, 4, and 6 hours post-dose on Day 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2017 (estimated)
  2. Study start13 Oct 2016
  3. Primary completion30 May 2017
  4. Study completion22 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03042910
Sponsor's protocol ID
MDV3800-14
Other IDs
C3441005
Status last verified
Dec 2019
First submitted
22 Dec 2016
Last updated
17 Dec 2019
Data monitoring committee
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Talazoparib in people with Solid Tumor, run by Pfizer at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time-matched Mean Change From Baseline in Corrected QT Intervals Based on the Fridericia's Correction Fomulation (QTcF) (time frame: 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03042910.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.

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