Open-Label Extension and Safety Study of Talazoparib

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02921919
Collaborator
Medivation, Inc. (Industry)
120
38
1
56.3
3.2
0.1

Study Details

Study Description

Brief Summary

This is a single-arm, open-label, extended treatment, safety study in patients treated with talazoparib in qualifying studies.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A SINGLE-ARM, OPEN-LABEL, MULTICENTER, EXTENDED TREATMENT, SAFETY STUDY IN PATIENTS TREATED WITH TALAZOPARIB
Actual Study Start Date :
Nov 8, 2016
Actual Primary Completion Date :
Jul 20, 2021
Actual Study Completion Date :
Jul 20, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Talazoparib

Drug: Talazoparib
Maximum starting dose: 1mg/day or last tolerated dose in the originating protocol
Other Names:
  • MDV3800
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death; inpatient hospitalization or prolongation of existing hospitalization; was life-threatening (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or was considered as an important medical event. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. AE included both SAEs and all non-SAEs. Treatment-related TEAEs were defined as any TEAE with at least a possible relationship to the study drug as assessed by the investigator or that was missing the assessment of causal relationship whose relationship to the study drug could not be ruled out.

    2. Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4 [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Severity was graded using NCI-CTCAE version 4 where, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs were reported.

    3. Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Number of participants with TEAEs leading to dose reduction, permanent study drug discontinuation and death were reported.

    4. Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      The following liver parameters were analyzed: aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBL) and alkaline phosphatase (ALP). The criteria for clinically significant abnormalities for liver parameters included AST or ALT greater than or equal to (>=) 3 times upper limit of normal (ULN); ALT or AST greater than (>) 5 times ULN; ALT or AST > 10 times ULN; ALT or AST > 20 times ULN; total TBL >2 times ULN; ALT or AST >= 3 times ULN and TBL > 2 times ULN and ALT or AST >= 3 times ULN and TBL > 2 times ULN and ALP < 2 times ULN.

    5. Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      The following hematology parameters were analyzed: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 and 4 toxicities were reported. Low indicates values lower than the normal range.

    6. Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      The following chemistry parameters were analyzed: alkaline phosphatase, bilirubin and creatinine. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 or 4 toxicities were reported. High indicates values higher than the normal range.

    7. Number of Participants With Clinically Significant Changes in Vital Signs and Weight [From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)]

      Criteria for clinically significant changes in vital signs included a) Systolic blood pressure (SBP): 1) absolute results >180 millimeter of mercury (mmHg) and increase from baseline >=40 mmHg, 2) absolute results <90 mmHg and decrease from baseline >30 mmHg; b) Diastolic blood pressure (DBP): 1) absolute results >110 mmHg and increase from baseline >=30 mmHg , 2) absolute results <50 mmHg and decrease from baseline >20 mmHg , 3) increase from baseline >=20 mmHg; c) Heart rate: 1) absolute results >120 beats per minute (bpm) and increase from baseline >30 bpm, 2) absolute results <50 bpm and >20 bpm decrease from baseline; d) Temperature: <=34.5 or >=38 degree Celsius. Criteria for clinically significant changes in weight: >10 percent (%) decrease from baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

    • Female patients of childbearing potential must have a negative pregnancy test before the first dose of talazoparib and must agree to use a highly effective birth control method from the time of the first dose of talazoparib through 45 days after the last dose.

    • 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 talazoparib through 105 days after the last dose. Contraception should be considered for a nonpregnant female partner of childbearing potential.

    • Female patients may not be breastfeeding at the first dose of talazoparib and must not breastfeed during study participation through 45 days after the last dose of talazoparib.

    Exclusion Criteria:
    • Permanently discontinued from any Medivation sponsored study with talazoparib alone or in combination with another agent.

    • Received an antineoplastic therapy or investigational agent after treatment with talazoparib in the originating protocol.

    • Has a clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, infectious, metabolic, neurologic, psychologic, or pulmonary disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator.

    • Diagnosis of myelodysplastic syndrome (MDS).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Hematology/Oncology - Alhambra Alhambra California United States 91801
    2 CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center Bakersfield California United States 93309
    3 UCLA Hematology/Oncology - Burbank Burbank California United States 91505
    4 St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare Fullerton California United States 92835
    5 UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D. Los Angeles California United States 90095-7349
    6 (IRB# 16-001189) Ronald Reagan UCLA Medical Center, Drug Information Center Los Angeles California United States 90095
    7 TRIO-US Central Administration Los Angeles California United States 90095
    8 UCLA Hematology/Oncology Los Angeles California United States 90095
    9 UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D. Los Angeles California United States 90095
    10 UCLA Hematology/Oncology - Pasadena Pasadena California United States 91105
    11 UCLA Hematology/Oncology - Porter Ranch Porter Ranch California United States 91326
    12 UCLA Hematology/Oncology - Santa Monica Santa Monica California United States 90404
    13 UCLA Torrance Oncology Torrance California United States 90505
    14 UCLA Hematology/Oncology - Santa Clarita Valencia California United States 91355
    15 Orlando Health, Inc. Orlando Florida United States 32806
    16 Memorial Hospital West Pembroke Pines Florida United States 33028
    17 IU Health Bloomington Hospital Bloomington Indiana United States 47403
    18 Fort Wayne Medical Oncology and Hematology, Inc. Fort Wayne Indiana United States 46804
    19 Fort Wayne Medical Oncology and Hematology, Inc. Fort Wayne Indiana United States 46845
    20 Indiana University Health Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    21 Investigational Drug Senvices Indianapolis Indiana United States 46202
    22 IU Health University Hospital Indianapolis Indiana United States 46202
    23 University of Michigan Health System Ann Arbor Michigan United States 48109
    24 Karmanos Cancer Institute Detroit Michigan United States 48201
    25 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    26 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    27 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    28 Juravinski Cancer Clinic Hamilton Ontario Canada L8L 8E7
    29 Jewish General Hospital Montreal Quebec Canada H3T 1E2
    30 Institut Paoli-Calmettes Marseille cedex 09 France 13273
    31 Frauenklinik des Universitaetsklinikums Erlangen Erlangen Germany 91054
    32 Magyar Honvedseg Egeszsegugyi Kozpont, Onkologiai Osztaly Budapest Hungary 1062
    33 Orszagos Onkologiai Intezet "B" Belgyogyaszati-Onkologiai Osztaly es Klinikai Farmakologiai Osztaly Budapest Hungary H-1122
    34 Arensia Exploratory Medicine, Institutia Medico-Sanitara Publica Institutul Oncologic Chisinau Moldova, Republic of MD-2025
    35 Szpital Lux Med Warszawa Poland 02-801
    36 FSBEI HE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF Moscow Russian Federation 119991
    37 Medical Technologies LLC Saint-Petersburg Russian Federation 196105
    38 Royal Marsden NHS Foundation Trust Sutton Surrey United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Pfizer
    • Medivation, Inc.

    Investigators

    • Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02921919
    Other Study ID Numbers:
    • MDV3800-13
    • C3441010
    • 2016-001972-31
    First Posted:
    Oct 3, 2016
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Eligible participants who received talazoparib as a single agent or in combination with another agent in following qualifying studies: PRP-001(NCT01286987), MDV3800-01(NCT02997163), MDV3800-02(NCT02997176), MDV3800-03(NCT03070548), MDV3800-04(NCT03077607), MDV3800-14(NCT03042910) continued therapy with talazoparib as single agent in this extended treatment study.
    Pre-assignment Detail A total of 120 participants were enrolled in the study of which 118 participants received the study treatment and 2 participants did not receive any study treatment as they were withdrawn before treatment initiation. Hence those 2 participants were not reported under any reporting arms.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of less than (<) 1 milligram (mg) orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Period Title: Overall Study
    STARTED 66 52
    Treated 66 52
    COMPLETED 0 0
    NOT COMPLETED 66 52

    Baseline Characteristics

    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day Total
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Total of all reporting groups
    Overall Participants 66 52 118
    Age, Customized (Count of Participants)
    < 50 years
    10
    15.2%
    9
    17.3%
    19
    16.1%
    50 to <65 years
    30
    45.5%
    17
    32.7%
    47
    39.8%
    >= 65 years
    25
    37.9%
    25
    48.1%
    50
    42.4%
    Missing
    1
    1.5%
    1
    1.9%
    2
    1.7%
    Sex: Female, Male (Count of Participants)
    Female
    46
    69.7%
    37
    71.2%
    83
    70.3%
    Male
    20
    30.3%
    15
    28.8%
    35
    29.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    6
    9.1%
    5
    9.6%
    11
    9.3%
    Not Hispanic or Latino
    56
    84.8%
    45
    86.5%
    101
    85.6%
    Unknown or Not Reported
    4
    6.1%
    2
    3.8%
    6
    5.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    3
    4.5%
    0
    0%
    3
    2.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    1.5%
    2
    3.8%
    3
    2.5%
    White
    59
    89.4%
    48
    92.3%
    107
    90.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    3
    4.5%
    2
    3.8%
    5
    4.2%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs
    Description An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death; inpatient hospitalization or prolongation of existing hospitalization; was life-threatening (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or was considered as an important medical event. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. AE included both SAEs and all non-SAEs. Treatment-related TEAEs were defined as any TEAE with at least a possible relationship to the study drug as assessed by the investigator or that was missing the assessment of causal relationship whose relationship to the study drug could not be ruled out.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 66 52
    TEAE
    63
    95.5%
    47
    90.4%
    SAE
    27
    40.9%
    18
    34.6%
    Treatment-related TEAEs
    45
    68.2%
    31
    59.6%
    Treatment-related SAEs
    6
    9.1%
    3
    5.8%
    2. Primary Outcome
    Title Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4
    Description An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Severity was graded using NCI-CTCAE version 4 where, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs were reported.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 66 52
    Count of Participants [Participants]
    38
    57.6%
    32
    61.5%
    3. Primary Outcome
    Title Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death
    Description An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Number of participants with TEAEs leading to dose reduction, permanent study drug discontinuation and death were reported.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 66 52
    TEAE leading to dose reduction
    6
    9.1%
    7
    13.5%
    TEAE leading to permanent study drug discontinuation
    5
    7.6%
    4
    7.7%
    TEAE leading to death
    7
    10.6%
    7
    13.5%
    4. Primary Outcome
    Title Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests
    Description The following liver parameters were analyzed: aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBL) and alkaline phosphatase (ALP). The criteria for clinically significant abnormalities for liver parameters included AST or ALT greater than or equal to (>=) 3 times upper limit of normal (ULN); ALT or AST greater than (>) 5 times ULN; ALT or AST > 10 times ULN; ALT or AST > 20 times ULN; total TBL >2 times ULN; ALT or AST >= 3 times ULN and TBL > 2 times ULN and ALT or AST >= 3 times ULN and TBL > 2 times ULN and ALP < 2 times ULN.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib. Here, "overall number of participants analyzed" signifies number of participants who were evaluable for this outcome measure.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 61 50
    ALT or AST >= 3*ULN
    5
    7.6%
    2
    3.8%
    ALT or AST > 5*ULN
    0
    0%
    0
    0%
    ALT or AST > 10*ULN
    0
    0%
    0
    0%
    ALT or AST > 20*ULN
    0
    0%
    0
    0%
    TBL > 2*ULN
    4
    6.1%
    0
    0%
    ALT or AST >= 3*ULN and TBL > 2*ULN (any visit date)
    2
    3%
    0
    0%
    ALT or AST >= 3*ULN and TBL > 2*ULN and ALP < 2*ULN (any visit date)
    0
    0%
    0
    0%
    5. Primary Outcome
    Title Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters
    Description The following hematology parameters were analyzed: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 and 4 toxicities were reported. Low indicates values lower than the normal range.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 66 52
    Hemoglobin (low): Grade 3
    7
    10.6%
    16
    30.8%
    Hemoglobin (low): Grade 4
    0
    0%
    0
    0%
    Leukocytes (low): Grade 3
    5
    7.6%
    2
    3.8%
    Leukocytes (low): Grade 4
    0
    0%
    0
    0%
    Lymphocytes (low): Grade 3
    11
    16.7%
    8
    15.4%
    Lymphocytes (low): Grade 4
    1
    1.5%
    1
    1.9%
    Neutrophils (low): Grade 3
    9
    13.6%
    4
    7.7%
    Neutrophils (low): Grade 4
    1
    1.5%
    0
    0%
    Platelets (low): Grade 3
    4
    6.1%
    4
    7.7%
    Platelets (low): Grade 4
    1
    1.5%
    1
    1.9%
    6. Primary Outcome
    Title Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters
    Description The following chemistry parameters were analyzed: alkaline phosphatase, bilirubin and creatinine. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 or 4 toxicities were reported. High indicates values higher than the normal range.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 66 52
    Alkaline Phosphatase (high): Grade 3
    5
    7.6%
    1
    1.9%
    Alkaline Phosphatase (high): Grade 4
    1
    1.5%
    0
    0%
    Bilirubin (high): Grade 3
    3
    4.5%
    0
    0%
    Bilirubin (high): Grade 4
    1
    1.5%
    0
    0%
    Creatinine (high): Grade 3
    1
    1.5%
    0
    0%
    Creatinine (high): Grade 4
    0
    0%
    0
    0%
    7. Primary Outcome
    Title Number of Participants With Clinically Significant Changes in Vital Signs and Weight
    Description Criteria for clinically significant changes in vital signs included a) Systolic blood pressure (SBP): 1) absolute results >180 millimeter of mercury (mmHg) and increase from baseline >=40 mmHg, 2) absolute results <90 mmHg and decrease from baseline >30 mmHg; b) Diastolic blood pressure (DBP): 1) absolute results >110 mmHg and increase from baseline >=30 mmHg , 2) absolute results <50 mmHg and decrease from baseline >20 mmHg , 3) increase from baseline >=20 mmHg; c) Heart rate: 1) absolute results >120 beats per minute (bpm) and increase from baseline >30 bpm, 2) absolute results <50 bpm and >20 bpm decrease from baseline; d) Temperature: <=34.5 or >=38 degree Celsius. Criteria for clinically significant changes in weight: >10 percent (%) decrease from baseline.
    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    Measure Participants 66 52
    SBP: absolute results >180 mmHg and increase from baseline >=40 mmHg
    1
    1.5%
    0
    0%
    SBP: absolute results <90 mmHg and decrease from baseline >30 mmHg
    1
    1.5%
    0
    0%
    DBP: absolute results >110 mmHg and increase from baseline >=30 mmHg
    0
    0%
    0
    0%
    DBP: absolute results <50 mmHg and decrease from baseline >20 mmHg
    0
    0%
    0
    0%
    DBP: increase from baseline >=20 mmHg
    6
    9.1%
    5
    9.6%
    Heart rate: absolute results >120 bpm and increase from baseline >30 bpm
    2
    3%
    0
    0%
    Heart rate: absolute results <50 bpm and decrease from baseline >20 bpm
    0
    0%
    0
    0%
    Temperature: <=34.5 or >=38 degree Celsius
    0
    0%
    0
    0%
    Weight: >10% decrease from baseline
    7
    10.6%
    2
    3.8%

    Adverse Events

    Time Frame From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
    Adverse Event Reporting Description An AE term may be reported as both a serious and non-serious AE, but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event. Safety population included all participants who received any amount of talazoparib.
    Arm/Group Title Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Arm/Group Description Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of < 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first.
    All Cause Mortality
    Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/66 (10.6%) 8/52 (15.4%)
    Serious Adverse Events
    Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/66 (40.9%) 18/52 (34.6%)
    Blood and lymphatic system disorders
    Anaemia 2/66 (3%) 2/52 (3.8%)
    Thrombocytopenia 2/66 (3%) 0/52 (0%)
    Cardiac disorders
    Bradycardia 1/66 (1.5%) 0/52 (0%)
    Supraventricular Tachycardia 0/66 (0%) 1/52 (1.9%)
    Gastrointestinal disorders
    Abdominal Pain 2/66 (3%) 0/52 (0%)
    Constipation 1/66 (1.5%) 0/52 (0%)
    Diarrhoea 1/66 (1.5%) 0/52 (0%)
    Dyspepsia 1/66 (1.5%) 0/52 (0%)
    Dysphagia 1/66 (1.5%) 0/52 (0%)
    Ileus 1/66 (1.5%) 1/52 (1.9%)
    Intestinal Obstruction 0/66 (0%) 1/52 (1.9%)
    Large Intestinal Obstruction 0/66 (0%) 1/52 (1.9%)
    Nausea 0/66 (0%) 1/52 (1.9%)
    Oesophagitis 1/66 (1.5%) 0/52 (0%)
    Small Intestinal Obstruction 1/66 (1.5%) 0/52 (0%)
    Vomiting 0/66 (0%) 1/52 (1.9%)
    General disorders
    Death 1/66 (1.5%) 0/52 (0%)
    Disease Progression 4/66 (6.1%) 0/52 (0%)
    Gait Disturbance 0/66 (0%) 1/52 (1.9%)
    General Physical Health Deterioration 0/66 (0%) 1/52 (1.9%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/66 (1.5%) 0/52 (0%)
    Jaundice 1/66 (1.5%) 0/52 (0%)
    Infections and infestations
    Abdominal Abscess 1/66 (1.5%) 0/52 (0%)
    Cellulitis 2/66 (3%) 0/52 (0%)
    Endocarditis Bacterial 0/66 (0%) 1/52 (1.9%)
    Pneumonia 1/66 (1.5%) 0/52 (0%)
    Sepsis 2/66 (3%) 0/52 (0%)
    Streptococcal Sepsis 0/66 (0%) 1/52 (1.9%)
    Urinary Tract Infection 1/66 (1.5%) 0/52 (0%)
    Urosepsis 1/66 (1.5%) 0/52 (0%)
    Injury, poisoning and procedural complications
    Fall 1/66 (1.5%) 0/52 (0%)
    Femur Fracture 1/66 (1.5%) 0/52 (0%)
    Hip Fracture 1/66 (1.5%) 0/52 (0%)
    Investigations
    Platelet Count Decreased 0/66 (0%) 1/52 (1.9%)
    Metabolism and nutrition disorders
    Failure To Thrive 0/66 (0%) 1/52 (1.9%)
    Gout 1/66 (1.5%) 0/52 (0%)
    Musculoskeletal and connective tissue disorders
    Muscular Weakness 0/66 (0%) 1/52 (1.9%)
    Pain In Extremity 0/66 (0%) 1/52 (1.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast Cancer 0/66 (0%) 2/52 (3.8%)
    Intraductal Proliferative Breast Lesion 0/66 (0%) 1/52 (1.9%)
    Leukaemia 1/66 (1.5%) 0/52 (0%)
    Malignant Pleural Effusion 1/66 (1.5%) 0/52 (0%)
    Ovarian Cancer 0/66 (0%) 3/52 (5.8%)
    Pericardial Effusion Malignant 0/66 (0%) 1/52 (1.9%)
    Nervous system disorders
    Aphasia 0/66 (0%) 1/52 (1.9%)
    Cauda Equina Syndrome 0/66 (0%) 1/52 (1.9%)
    Cerebrovascular Accident 1/66 (1.5%) 1/52 (1.9%)
    Paraesthesia 1/66 (1.5%) 0/52 (0%)
    Renal and urinary disorders
    Hydronephrosis 1/66 (1.5%) 0/52 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 3/66 (4.5%) 1/52 (1.9%)
    Haemoptysis 0/66 (0%) 1/52 (1.9%)
    Respiratory Failure 1/66 (1.5%) 0/52 (0%)
    Other (Not Including Serious) Adverse Events
    Initial Dose Talazoparib: < 1 mg/Day Initial Dose Talazoparib: 1 mg/Day
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 54/66 (81.8%) 46/52 (88.5%)
    Blood and lymphatic system disorders
    Anaemia 19/66 (28.8%) 18/52 (34.6%)
    Iron Deficiency Anaemia 0/66 (0%) 3/52 (5.8%)
    Neutropenia 10/66 (15.2%) 4/52 (7.7%)
    Thrombocytopenia 10/66 (15.2%) 5/52 (9.6%)
    Gastrointestinal disorders
    Abdominal Distension 4/66 (6.1%) 1/52 (1.9%)
    Abdominal Pain 9/66 (13.6%) 5/52 (9.6%)
    Abdominal Pain Upper 5/66 (7.6%) 2/52 (3.8%)
    Constipation 8/66 (12.1%) 2/52 (3.8%)
    Diarrhoea 8/66 (12.1%) 3/52 (5.8%)
    Nausea 18/66 (27.3%) 10/52 (19.2%)
    Vomiting 12/66 (18.2%) 4/52 (7.7%)
    General disorders
    Asthenia 6/66 (9.1%) 6/52 (11.5%)
    Fatigue 17/66 (25.8%) 11/52 (21.2%)
    Oedema Peripheral 7/66 (10.6%) 4/52 (7.7%)
    Pain 0/66 (0%) 3/52 (5.8%)
    Infections and infestations
    Upper Respiratory Tract Infection 8/66 (12.1%) 3/52 (5.8%)
    Urinary Tract Infection 6/66 (9.1%) 2/52 (3.8%)
    Injury, poisoning and procedural complications
    Fall 6/66 (9.1%) 1/52 (1.9%)
    Investigations
    Blood Creatinine Increased 3/66 (4.5%) 3/52 (5.8%)
    Neutrophil Count Decreased 4/66 (6.1%) 4/52 (7.7%)
    Platelet Count Decreased 2/66 (3%) 9/52 (17.3%)
    Weight Decreased 3/66 (4.5%) 3/52 (5.8%)
    White Blood Cell Count Decreased 6/66 (9.1%) 3/52 (5.8%)
    Metabolism and nutrition disorders
    Decreased Appetite 7/66 (10.6%) 7/52 (13.5%)
    Hypokalaemia 5/66 (7.6%) 1/52 (1.9%)
    Hypomagnesaemia 1/66 (1.5%) 3/52 (5.8%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/66 (9.1%) 4/52 (7.7%)
    Back Pain 10/66 (15.2%) 2/52 (3.8%)
    Myalgia 4/66 (6.1%) 1/52 (1.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant Ascites 0/66 (0%) 3/52 (5.8%)
    Nervous system disorders
    Dizziness 5/66 (7.6%) 0/52 (0%)
    Headache 7/66 (10.6%) 0/52 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 7/66 (10.6%) 4/52 (7.7%)
    Dyspnoea 8/66 (12.1%) 6/52 (11.5%)
    Skin and subcutaneous tissue disorders
    Alopecia 6/66 (9.1%) 5/52 (9.6%)
    Vascular disorders
    Hypertension 4/66 (6.1%) 2/52 (3.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02921919
    Other Study ID Numbers:
    • MDV3800-13
    • C3441010
    • 2016-001972-31
    First Posted:
    Oct 3, 2016
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Jul 1, 2022