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A Study of Talazoparib in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070548
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : December 17, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 24, 2017
First Posted Date  ICMJE March 3, 2017
Results First Submitted Date  ICMJE May 25, 2018
Results First Posted Date  ICMJE December 17, 2018
Last Update Posted Date December 17, 2018
Actual Study Start Date  ICMJE September 2016
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
  • Maximum Observed Plasma Concentration (Cmax) of Talazoparib [ Time Frame: 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 ]
  • Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib [ Time Frame: 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 ]
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Talazoparib [ Time Frame: 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 ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf).
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib [ Time Frame: 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 ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration.
  • Terminal Elimination Half-Life (t1/2) of Talazoparib [ Time Frame: 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 ]
    Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half.
  • Apparent Total Plasma Clearance (CL/F) of Talazoparib [ Time Frame: 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 ]
    Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
  • Apparent Volume of Distribution (Vd/F) of Talazoparib [ Time Frame: 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 ]
    Apparent 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 the drug.
  • Maximum Observed Plasma Concentration (Cmax) of 14C- Radioactivity [ Time Frame: 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 ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Time to Attain Maximum Observed Plasma Concentration (Tmax) of 14C- Radioactivity [ Time Frame: 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 ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity [ Time Frame: 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 ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity [ Time Frame: 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 ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Terminal Elimination Half-Life (t1/2) of 14C- Radioactivity in Plasma [ Time Frame: 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 ]
    Terminal elimination half-life was defined as the time measured for the plasma radioactivity concentration to decrease by one half. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Apparent Total Plasma Clearance (CL/F) of 14C- Radioactivity [ Time Frame: 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 ]
    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Plasma [ Time Frame: 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 ]
    Apparent 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. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Maximum Observed Whole Blood Concentration (Cmax) of 14C- Radioactivity [ Time Frame: 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 ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Time to Attain Maximum Observed Whole Blood Concentration (Tmax) of 14C- Radioactivity [ Time Frame: 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 ]
    100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity [ Time Frame: 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 ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity [ Time Frame: 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 ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Apparent Total Whole Blood Clearance (CL/F) of 14C- Radioactivity [ Time Frame: 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 ]
    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Whole Blood [ Time Frame: 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 ]
    Apparent 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 the drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Amount of Talazoparib Excreted in Urine During Each Collection Interval (Ae t1-t2) [ Time Frame: 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 ]
    Ae t1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2).
  • Percentage of Dose of Talazoparib Excreted During Each Collection Interval (Aet1-t2%) of Talazoparib [ Time Frame: 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 ]
    Aet1-t2% was the percentage of Aet1-t2, where Aet1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2).
  • Renal Clearance (CLr) of Talazoparib [ Time Frame: 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 ]
    Renal clearance was calculated as cumulative amount of drug excreted in urine divided by AUC(0-last) (area under the plasma concentration-time curve from zero to the time of the last measurable concentration).
  • The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose [ Time Frame: 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 ]
    Recovery of 14C-radioactivity in urine and feces was calculated in terms of percentage of administered dose after administration of a single 1 mg dose of oral solution (containing 100 micro-curie 14C-labeled talazoparib).
Original Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Excretion of 14C radioactivity in urine and feces measured as time course of excretion [ Time Frame: Approximately 10 months following first patient enrolled ]
  • The recovery of 14C radioactivity measured as a percentage of the administered dose. [ Time Frame: Approximately 10 months following first patient enrolled ]
  • Cmax of talazoparib [ Time Frame: Approximately 10 months following first patient enrolled ]
  • Tmax of talazoparib [ Time Frame: Approximately 10 months following first patient enrolled ]
  • AUC of talazoparib [ Time Frame: Approximately 10 months following first patient enrolled ]
  • t1/2 of talazoparib [ Time Frame: Approximately 10 months following first patient enrolled ]
  • CL/F of talazoparib [ Time Frame: Approximately 10 months following first patient enrolled ]
  • Vd/F of talazoparib [ Time Frame: Approximately 10 months following first patient enrolled ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
  • Ratio of Maximum Observed Plasma Concentration to Maximum Observed Whole Blood Concentration for 14C- Radioactivity [ Time Frame: 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 ]
    100 micro-curie of 14C radiolabeled talazoparib was present in 1 mg of talazoparib.
  • 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 [ Time Frame: 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 ]
    AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • 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 [ Time Frame: 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 ]
    AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.
  • Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: 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) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug through 14 days after the last day of mass balance phase and at least 30 days after Day 1 or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first (up to maximum duration of 8 weeks from screening to follow-up for each participant) or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-serious (AEs) and serious adverse events (SAEs).
  • Number of Participants With Clinically Significant Vital Signs Parameters [ Time Frame: Baseline up to Day 22 ]
    Vital Signs included heart rate, respiratory rate, body temperature, systolic blood pressure and diastolic blood pressure. clinical significance of vital signs was determined at the investigator's discretion.
  • Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline up to Day 22 ]
    Criteria for clinically significant ECG abnormalities : Heart Rate; increase from baseline greater than (>)25 %and to a value >100, decrease from baseline >25% and to a value < 50; PR Interval: increase from baseline >25% and to a value >200; QRS Duration: increase from baseline >25% and to a value >100; QT interval using Fridericia's correction (QTcF): ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec; QT Interval: ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec.
  • Number of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: Baseline up to Day 22 ]
    Haematological, biochemistry and urinalysis parameters. Biochemistry parameters:alkaline phosphatase 30-120units per liter(U/L), creatinine 53-110micromole/L(micromol/L), gamma glutamyl transferase 7-50U/L, glucose 3.3-5.5millimoles/L(mmol/L), lactate dehydrogenase 200-460U/L, triglycerides 0.4-1.7mmol/L, cholesterol 2.6-5.2mmol/L, phosphate 0.8-1.45mmol/L, sodium 135-146mmol/L, urea 2.8-7.2mmol/L, chloride 95-109mmol/L, creatine kinase 24-170U/L, aspartate aminotransferase 4-46U/L, potassium 3.5-5.5mmol/L. Haematology parameters:haemoglobin 120-155 gram/L(g/L), erythrocytes 4-5.2 10^12/L, haematocrit 0.35-0.45, prothrombin time 13.7-15.6 second(sec), lymphocytes 1-3.7 10^9/L, platelets 150-400 10^9/L, prothrombin intl. normalized ratio 0.89-1.1, activated partial thromboplastin time 25-43 sec, basophils 0-0.09 10^9/L, neutrophils 1.5-7 10^9/L, and leukocytes 4-10 10^9/L. Urinalysis parameters:urinalysis specific gravity 1.012-1.03, urinalysis pH 4.8-7.8.
  • Number of Participants With Change From Baseline in Physical Examination Findings [ Time Frame: Baseline up to Day 22 ]
    Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin/subcutaneous tissue and thorax/lungs.
  • Amount of Any Significant Metabolites of Talazoparib in Urine and Feces [ Time Frame: 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 ]
    M4 (M481/1, cysteine conjugate of mono-desfluoro-talazoparib) metabolite was found in urine. MDV10595 (M1, dehydrogenated talazoparib (PF-07052386), M556/1 (glucuronide conjugate of talazoparib), and M2 (M396/1, mono-oxidative talazoparib) metabolites were calculated together and were also found in urine. Three metabolites named as: MDV10595 (M1)/M556/1 and M2 (M396/1) which were calculated together were detected in feces. Amount of metabolite in this outcome measure was measured in terms of percentage of dose of talazoparib.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Safety and tolerability measured as summary of AEs, physical examinations (and weight), vital signs, electrocardiograms (ECGs), and laboratory evaluations [ Time Frame: Approximately 10 months following first patient enrolled ]
  • 14C radioactivity of talazoparib in erythrocytes and whole blood measured as percentage to plasma [ Time Frame: Approximately 10 months following first patient enrolled ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Talazoparib in Patients With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Open-label Study Of 14c-labeled Talazoparib In Patients With Advanced Solid Tumors
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..
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Drug: Talazoparib
1 mg of talazoparib containing100 μCi of 14C-radiolabeled talazoparib
Other Names:
  • MDV3800
  • BMN673
Study Arms  ICMJE Experimental: ADME
1 mg talazoparib containing100 μCi of 14C-radiolabeled talazoparib
Intervention: Drug: Talazoparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 28, 2017)
6
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2017
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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]).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hungary
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03070548
Other Study ID Numbers  ICMJE MDV3800-03
C3441003 ( Other Identifier: Alias Study Number )
2016-001394-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Medivation, Inc.
Investigators  ICMJE
Study Director: Pfizer Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP