Open-Label Extension and Safety Study of Talazoparib
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
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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.- MDV3800-13
- C3441010
- 2016-001972-31
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
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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
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 |
ClinicalTrials.gov_Inquiries@pfizer.com |
- MDV3800-13
- C3441010
- 2016-001972-31