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Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors

Primary Purpose

Advanced or Recurrent Solid Tumors, Breast Neoplasms, Ovarian Cancer, Epithelial

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Talazoparib

About this trial

This is an interventional treatment trial for Advanced or Recurrent Solid Tumors focused on measuring BRCA1 Protein, BRCA2 Protein

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor
Must have available archived tumor tissue (formalin-fixed paraffin-embedded) [FFPE].
18 years of age or older.
Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9 (pancreatic cancer).
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Have adequate organ function
Able to take oral medications.
Willing and able to provide informed consent.
Sexually active patients must be willing to use an acceptable method of contraception.
Females of childbearing potential must have a negative serum pregnancy test at screening.
Willing and able to comply with all study procedures.

Part 2 Dose Expansion Tumor Types:

Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 4 prior regimens for metastatic disease.
Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 2 prior regimens for metastatic disease.
Small cell lung cancer (SCLC) patients who have received no more than one prior regimen for SCLC.
Ewing's sarcoma patients who have received no more than 3 prior regimens for metastatic disease.

Exclusion Criteria:

Part 2 Expansion: Prior treatment with a PARP inhibitor.
Has history of central nervous system (CNS) metastasis.
* Exception: In patients with SCLC, history of adequately treated brain metastasis who do not require corticosteroids for management of CNS symptoms.
Has had major surgery within 28 days before Cycle 1, Day 1.
Has active peptic ulcer disease.
Active gastrointestinal tract disease with malabsorption syndrome.
Pregnant or breastfeeding at screening or planning to become pregnant (in each case, either oneself or one's partner) at any time during the study.

Sites / Locations

Scottsdale Healthcare
Virginia G. Piper Cancer Center Research Pharmacy
(IRB# 12-000131) Ronald Reagan UCLA Medical Center, Drug Information Center
Ronald Reagan UCLA Medical Center
UCLA Hematology/Oncology
Westwood Bowyer Clinic, Peter Morton Medical Building
Santa Monica - UCLA Medical Center & Orthopaedic Hospital
UCLA Hematology/Oncology - Santa Monica
IU Health Bloomington Hospital
Indiana University Health Melvin and Bren Simon Cancer Center
Investigational Drug Services
IU Health University Hospital
University of Michigan Health System
The University of Texas MD Anderson Cancer Center
Royal Marsden Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Talazoparib

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Objective Response

Objective response in participants was defined as the number of participants with complete response (CR) or partial response (PR) after treatment with talazoparib and maintained for at least 4 weeks (28 days) as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1. CR defined as disappearance of all non-nodal target lesions (where all target lesions were recorded with a length of 0 millimeter [mm] on the case report form [CRF]) and the reduction of the shortest diameter of all nodal lesions to less than [<] 10 mm. PR was defined by a 30% or more decrease in the sum of the longest diameters (SLD) + sum of shortest diameters (SSD) of target lesions, taking as reference the baseline SLD+SSD.

Number of Participants With Best Overall Response

Best overall response: best response (in the order of confirmed CR, confirmed PR, stable disease [SD] and progressive disease [PD]) among all overall response as RECIST 1.1, recorded from date of first dose of talazoparib until participant withdrew from study/data cut-off date, whichever earlier. CR defined as disappearance of all non-nodal target lesions (where all target lesions recorded with a length of 0 mm on the CRF) and the reduction of the shortest diameter of all nodal lesions to < 10 mm. PR defined as at least a 30% decrease in sum of the diameters of target lesions, reference to baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).

Progression-Free Survival (PFS)

PFS was defined as the time (in weeks) from the date of first dose of study drug to the earlier date of the documented PD or death due to any cause. PD as per RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).

Duration of Response

Duration of response was defined as the time (in weeks) from the date of the first documented objective response confirmed at least 28 days later to the date of the first documented PD or date of death, whichever occurred first. PD as per RECIST version 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).

Number of Participants With Stable Disease

SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).

Part 1: Maximum Tolerated Dose (MTD)

The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose Limiting Toxicity (DLT). DLT defined as any of the following occurring during cycle 1 of part 1 of study, Hematologic toxicity: Any grade 4 or higher hematologic adverse event, Grade 3 thrombocytopenia associated with grade 2 or higher haemorrhage, Grade 3 thrombocytopenia or neutropenia that led to interruption of dosing for 5 or more days. Nonhematologic toxicity: grade 3 or higher laboratory AE which was asymptomatic and rapidly reversible adverse events (returned to baseline or to grade 1 or lower within 7 days), Grade 3 nausea, vomiting, or diarrhea that could be medically managed to grade 2 or lower with anti-emetics and/or anti-diarrheals within 24 hours, Grade 3 fatigue that improved to grade 2 or lower in 5 days or less, Alopecia. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Part 1: Recommended Part 2 Dose of Talazoparib

The Recommended dose of talazoparib for use in Part 2 was determined in Part 1 (dose escalation) on the basis of the totality of safety, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.

Secondary Outcome Measures

Full Information

NCT ID

NCT01286987

First Posted

January 26, 2011

Last Updated

June 29, 2018

Sponsor

Pfizer

Collaborators

Medivation, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01286987

Brief Title

Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors

Official Title

A Phase 1, First In Human, Single-arm, Open-label Study Of Once A Day, Orally Administered Talazoparib (Bmn 673) In Patients With Advanced Or Recurrent Solid Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Completed

Study Start Date

January 3, 2011 (Actual)

Primary Completion Date

March 31, 2015 (Actual)

Study Completion Date

January 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

Collaborators

Medivation, Inc.

4. Oversight

5. Study Description

Brief Summary

This is a single-arm, open-label study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of talazoparib in patients with advanced tumors with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation phase in which the maximum tolerated dose will be defined, and a dose expansion phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced or Recurrent Solid Tumors, Breast Neoplasms, Ovarian Cancer, Epithelial, Ewing Sarcoma, Small Cell Lung Carcinoma, Prostate Cancer, Pancreas Cancer

Keywords

BRCA1 Protein, BRCA2 Protein

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Masking

None (Open Label)

Enrollment

113 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Talazoparib

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Talazoparib

Other Intervention Name(s)

BMN 673, MDV3800

Intervention Description

Oral capsule with multiple dosage forms given once daily

Primary Outcome Measure Information:

Title

Number of Participants With Objective Response

Description

Time Frame

From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Title

Number of Participants With Best Overall Response

Description

Time Frame

From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Title

Progression-Free Survival (PFS)

Description

Time Frame

Baseline, until PD or death due to any cause (maximum duration:1071 days for Part 1; 834 days for Part 2)

Title

Duration of Response

Description

Time Frame

Baseline until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Title

Number of Participants With Stable Disease

Description

Time Frame

Baseline, until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)

Title

Part 1: Maximum Tolerated Dose (MTD)

Description

Time Frame

Cycle 1 (Day 1 up to Day 42)

Title

Part 1: Recommended Part 2 Dose of Talazoparib

Description

Time Frame

Baseline up to Cycle 50 (each cycle 28 days)

Other Pre-specified Outcome Measures:

Title

Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events

Description

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study (up to 1071 days for Part 1 and up to 834 days for Part 2) that were absent before treatment or that worsened relative to pre-treatment state.

Time Frame

Part 1: Baseline up to 1071 days; Part 2: Baseline up to 834 days

Title

Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Title

Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib

Time Frame

Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1

Title

Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Title

Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib

Time Frame

Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1

Title

Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib

Description

Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last).

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1

Title

Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib

Description

Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last).

Time Frame

Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1

Title

Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 35

Title

Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib

Description

AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1

Title

Part 1: Terminal Half-Life (t1/2) of Talazoparib

Description

T1/2 is the time measured for the plasma concentration of talazoparib to decrease by one half.

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

Title

Part 1: Apparent Oral Clearance (CL/F) of Talazoparib

Description

Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed.

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1

Title

Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib

Description

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was influenced by the fraction absorbed.

Time Frame

Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor Must have available archived tumor tissue (formalin-fixed paraffin-embedded) [FFPE]. 18 years of age or older. Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9 (pancreatic cancer). Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Have adequate organ function Able to take oral medications. Willing and able to provide informed consent. Sexually active patients must be willing to use an acceptable method of contraception. Females of childbearing potential must have a negative serum pregnancy test at screening. Willing and able to comply with all study procedures. Part 2 Dose Expansion Tumor Types: Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 4 prior regimens for metastatic disease. Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 2 prior regimens for metastatic disease. Small cell lung cancer (SCLC) patients who have received no more than one prior regimen for SCLC. Ewing's sarcoma patients who have received no more than 3 prior regimens for metastatic disease. Exclusion Criteria: Part 2 Expansion: Prior treatment with a PARP inhibitor. Has history of central nervous system (CNS) metastasis. * Exception: In patients with SCLC, history of adequately treated brain metastasis who do not require corticosteroids for management of CNS symptoms. Has had major surgery within 28 days before Cycle 1, Day 1. Has active peptic ulcer disease. Active gastrointestinal tract disease with malabsorption syndrome. Pregnant or breastfeeding at screening or planning to become pregnant (in each case, either oneself or one's partner) at any time during the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Medivation, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Scottsdale Healthcare

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85258

Country

United States

Facility Name

Virginia G. Piper Cancer Center Research Pharmacy

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85258

Country

United States

Facility Name

(IRB# 12-000131) Ronald Reagan UCLA Medical Center, Drug Information Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Ronald Reagan UCLA Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

UCLA Hematology/Oncology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Westwood Bowyer Clinic, Peter Morton Medical Building

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Santa Monica - UCLA Medical Center & Orthopaedic Hospital

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

UCLA Hematology/Oncology - Santa Monica

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

IU Health Bloomington Hospital

City

Bloomington

State/Province

Indiana

ZIP/Postal Code

47403

Country

United States

Facility Name

Indiana University Health Melvin and Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Investigational Drug Services

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

IU Health University Hospital

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

University of Michigan Health System

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

The University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4009

Country

United States

Facility Name

Royal Marsden Hospital NHS Foundation Trust

City

Sutton

State/Province

Surrey

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors

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