Clinical trial NCT03070548: A Study of Talazoparib in Patients With Advanced Solid Tumors
Official title: A Phase 1 Open-label Study Of 14c-labeled Talazoparib In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2017-03-03
Enrollment: 6
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 study will evaluate the mass balance of talazoparib after a single dose of talazoparib.

Detailed description: Patients participating in this study with no clinically significant toxicities may be eligible to continue treatment on a separate extension protocol after discussion with the Principal Investigator and obtaining Sponsor permission..

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age and willing and able to provide informed consent.
2. Histologically confirmed advanced solid tumor (limited to platinum-resistant ovarian carcinoma, cervical adenocarcinoma, small cell lung carcinoma or triple-negative breast cancer) judged by the Investigator to not be appropriate for standard therapy.
3. Eastern Co-Operative Oncology Group (ECOG) performance status ≤ 2 at screening and Day -1.
4. Expected life expectancy of ≥ 3 months.
5. Able to swallow the study drug and comply with study requirements.
6. Female subjects may be enrolled if they are considered not of childbearing potential, or who are post-menopausal, or of childbearing potential using a highly effective form of contraception, and female subjects should not donate eggs from the time point of IMP administration until at least 45 days thereafter.
7. Males with partners of childbearing potential may be enrolled if they use a condom when having sex with a pregnant woman or with a woman of childbearing potential from 21 days before the first dose of study drug through 105 days after the last dose of study drug, and males should not donate sperm from the time point of study drug administration until at least 105 days thereafter.
8. Female patients must not be breastfeeding at screening and during the study participation until 45 days after the last dose of the study drug.
9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Treatment within 14 weeks or five half-live prior to dosing with any type of systemic anticancer therapy or any investigational agent, whichever is longer.
2. Major surgery within 8 weeks before screening.
3. Serious accompanying disorder or impaired organ function.
4. Symptomatic or impending spinal cord compression or cauda equina syndrome.
5. Non-healing wound, ulcer, or bone fracture, not including a pathological bone fracture caused by a pre-existent pathological bone lesion.
6. Known myelodysplastic syndrome.
7. Patients with the following serologies should be excluded: HBsAg+ or anti-HBc+; HCV+; HIV+.
8. Serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
9. Gastrointestinal disorder affecting absorption.
10. Known hypersensitivity to any of the talazoparib solution components.
11. Use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BRCP within 7 days or 5 half-lives, whichever is longer, before Day 1.
12. Any condition or reason that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Sponsor (e.g. non-compliance, excessive alcohol consumption, intake of drugs of abuse unless these drugs are medically indicated \[e.g. opiates for pain relief\]).

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Terminal Elimination Half-Life (t1/2) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Apparent Total Plasma Clearance (CL/F) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Apparent Volume of Distribution (Vd/F) of Talazoparib
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Time to Attain Maximum Observed Plasma Concentration (Tmax) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Terminal Elimination Half-Life (t1/2) of 14C- Radioactivity in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Apparent Total Plasma Clearance (CL/F) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Maximum Observed Whole Blood Concentration (Cmax) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Time to Attain Maximum Observed Whole Blood Concentration (Tmax) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Apparent Total Whole Blood Clearance (CL/F) of 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Whole Blood
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Amount of Talazoparib Excreted in Urine During Each Collection Interval (Ae t1-t2)
timeFrame: Pre-dose, 0 to 8 hours (hrs), 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose
measure: Percentage of Dose of Talazoparib Excreted During Each Collection Interval (Aet1-t2%) of Talazoparib
timeFrame: Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose
measure: Renal Clearance (CLr) of Talazoparib
timeFrame: Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose
measure: The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose
timeFrame: From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose
Secondary outcomes:
measure: Ratio of Maximum Observed Plasma Concentration to Maximum Observed Whole Blood Concentration for 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity for 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable for 14C- Radioactivity
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: Day 1 to 14 days after last day of mass balance phase and at least 30 days after Day1/before initiation of new cytotoxic chemotherapy, new investigational treatment/first day of extension protocol, whichever occurs first(up to maximum duration of 8 weeks)
measure: Number of Participants With Clinically Significant Vital Signs Parameters
timeFrame: Baseline up to Day 22
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to Day 22
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline up to Day 22
measure: Number of Participants With Change From Baseline in Physical Examination Findings
timeFrame: Baseline up to Day 22
measure: Amount of Any Significant Metabolites of Talazoparib in Urine and Feces
timeFrame: From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: PRA Magyarorszag Kft, Fazis I-es Klinikai Farmakologiai Vizsgalohely
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: