Clinical trial NCT01286987: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2011-02-01
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Objective Response
timeFrame: From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
measure: Number of Participants With Best Overall Response
timeFrame: From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline, until PD or death due to any cause (maximum duration:1071 days for Part 1; 834 days for Part 2)
measure: Duration of Response
timeFrame: Baseline until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
measure: Number of Participants With Stable Disease
timeFrame: Baseline, until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
measure: Part 1: Maximum Tolerated Dose (MTD)
timeFrame: Cycle 1 (Day 1 up to Day 42)
measure: Part 1: Recommended Part 2 Dose of Talazoparib
timeFrame: Baseline up to Cycle 50 (each cycle 28 days)
Secondary outcomes:
Other outcomes:
measure: Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: Part 1: Baseline up to 1071 days; Part 2: Baseline up to 834 days
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
timeFrame: 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
measure: Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
timeFrame: Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
timeFrame: 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
measure: Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
timeFrame: Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
measure: 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
timeFrame: 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
measure: 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
timeFrame: Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
measure: Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib
timeFrame: 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
measure: Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib
timeFrame: 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
measure: Part 1: Terminal Half-Life (t1/2) of Talazoparib
timeFrame: 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
measure: Part 1: Apparent Oral Clearance (CL/F) of Talazoparib
timeFrame: 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
measure: Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib
timeFrame: 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
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center Research Pharmacy
state: Arizona
city: Los Angeles
country: United States
facility: (IRB# 12-000131) Ronald Reagan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Los Angeles
country: United States
facility: Westwood Bowyer Clinic, Peter Morton Medical Building
state: California
city: Santa Monica
country: United States
facility: Santa Monica - UCLA Medical Center & Orthopaedic Hospital
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Bloomington
country: United States
facility: IU Health Bloomington Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Drug Services
state: Indiana
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital NHS Foundation Trust
state: Surrey
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
affiliation: Medivation, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: