Clinical trial NCT02997176: An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)
Official title: A PHASE I OPEN-LABEL PHARMACOKINETICS AND SAFETY STUDY OF TALAZOPARIB (MDV3800) IN PATIENTS WITH ADVANCED SOLID TUMORS AND NORMAL OR VARYING DEGREES OF HEPATIC IMPAIRMENT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2016-12-19
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.

Detailed description: At the end of the study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study. The decision to allow the patient to continue dosing with talazoparib in an open-label extension (OLE) study will be based on potential overall benefit-risk and patient meeting eligibility criteria for OLE.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations).
2. Female or male at least 18 years of age.
3. Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
4. Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
5. Expected life expectancy of ≥ 3 months.
6. Able to swallow the study drug (no contraindication to oral agents).
7. Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
8. Adequate other organ function at screening and enrollment.
9. Female patients of childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception from the time of the first dose of study drug through 7 months after the last dose of study drug.
10. Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 4 months after last dose of study drug.
11. Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the study drug.
12. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Treatment within 14 days or five half lives prior to enrollment whichever is longer with any type of systemic anticancer-therapy or any investigational drug
2. Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
3. Major surgery within 28 days prior to enrollment.
4. Serious accompanying cardiac disorder
5. Active known or suspected brain metastasis or active leptomeningeal disease needing treatment
6. Symptomatic or impending spinal cord compression or cauda equine syndrome
7. Has undergone a liver transplant, kidney transplant or nephrectomy.
8. Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.
9. Known myelodysplastic syndrome
10. Seropositive for human immunodeficiency virus (HIV).
11. Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
12. Gastrointestinal disorder affecting absorption.
13. Known or suspected hypersensitivity to any of the talazoparib capsule components.
14. Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor

Primary outcomes:
measure: Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Secondary outcomes:
measure: Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1
timeFrame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
measure: Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1
timeFrame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1
timeFrame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
measure: Fraction of Unbound (fu) Plasma Talazoparib on Day 1
timeFrame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
measure: Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1
timeFrame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
measure: Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1
timeFrame: Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1
measure: Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22
timeFrame: Pre-dose on Day 8, 15 and 22
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Fraction of Unbound (fu) Plasma Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Accumulation Ratio (Rac) of Plasma Talazoparib
timeFrame: Pre-dose (within 60 minutes prior to dose) on Day 1, pre-dose(24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose) on Day 22 and 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Days 1 and 22
measure: Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22
timeFrame: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
measure: Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1
timeFrame: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
measure: Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1
timeFrame: A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1
measure: Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22
timeFrame: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22
measure: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22
timeFrame: Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22
measure: Renal Clearance (CLr) of Talazoparib on Day 22
timeFrame: Ae: Post-dose at any time between 0 to 12, 12 to 24 hrs on Day 22; AUC0-24: Pre-dose (24 hrs +/- 60 minutes from previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, any time between 8 to12, 24 hrs post-dose on Day 22
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study
timeFrame: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
measure: Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study
timeFrame: Baseline, Day 2, 8, 15, 22 and End of Study (Day 52)
measure: Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study
timeFrame: Baseline, Day 8, 15, 22 and End of Study (Day 52)
measure: Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study
timeFrame: Baseline, Day 8, 15, 22 and End of Study (Day 52)
measure: Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Screening (2 to 28 days prior to Day 1), Day -1 (1 day prior to Day 1), safety follow up (Visit up to Day 52)
Other outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Number of Participants With TEAEs Leading to Study Drug Discontinuation
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Number of Participants With TEAEs Resulting in Death
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Number of Participants With Treatment Emergent Treatment Related Adverse Events and SAEs
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
Locations:
city: Alhambra
country: United States
facility: UCLA Hematology/Oncology - Alhambra
state: California
city: Bakersfield
country: United States
facility: CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Fullerton
country: United States
facility: St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Porter Ranch
country: United States
facility: UCLA Hematology/Oncology - Porter Ranch
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Torrance
country: United States
facility: UCLA Torrance Oncology
state: California
city: Valencia
country: United States
facility: UCLA Hematology/Oncology - Santa Clarita
state: California
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: