Clinical trial NCT02997163: An Open-Label Pharmacokinetics and Safety Study of Talazoparib
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 RENAL 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: 34
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 trial will investigate the pharmacokinetics (PK) and safety of talazoparib in patients with advanced solid tumors and impaired renal 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 after discussion with the Principal Investigator and obtaining Sponsor permission. Sponsor decision to allow the patient to continue dosing with talazoparib in an open-label extension study will be based on potential overall benefit-risk, patient acceptance and other relevant criteria.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent form (by the patient or a legally acceptable representative as per the local regulations) obtained prior to initiation of any study-specific procedure and treatment.
2. Female or male of at least 18 years of age.
3. Histologically or cytologically confirmed advanced solid tumor with no available standard approved treatment options in the opinion of the Investigator
4. Eastern Cooperative Oncology Group (ECOG) Performance status (PS) ≤ 2.
5. Expected life expectancy of ≥ 3 months.
6. Able to swallow the study drug (no contra indication to oral agents).
7. Renal function at screening and enrollment as defined by the Modification of Diet in Renal Disease (MDRD) equation.
8. Patient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records.
9. Patient is not currently on hemodialysis and/or peritoneal dialysis for management of chronic kidney disease or acute failure/conditions.
10. Patient has no unstable renal function, defined as a change in estimated glomerular filtration rate (eGFR) (calculated with the MDRD equation) of \> 25% for patients with mild and moderate renal impaired or as a change in eGFR \> 30% for patients with severe renal impaired, from screening to enrollment.
11. Adequate other organ function at screening and enrollment.
12. Female patients of childbearing potential must have a negative serum pregnancy test at screening, and must agree to use a highly effective birth control method from the time of the first dose of study drug through 45 days after the last dose of study drug.
13. 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 105 days after last dose of study drug.
14. Female patients must not be breastfeeding at screening nor during the study participation until 45 days after the last dose of study drug.
15. 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 with any type of systemic anticancer-therapy or any investigational drug, whichever is longer.
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 undergoing or requiring treatment.
6. Symptomatic or impending spinal cord compression or cauda equina 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: Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
measure: Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
measure: Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
measure: Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Secondary outcomes:
measure: Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
measure: Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
measure: Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
measure: Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
measure: Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
measure: Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1
measure: Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
measure: Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib
timeFrame: Predose on Day 22
measure: Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
measure: Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24)
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22
measure: Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22
measure: Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22
measure: Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24)
timeFrame: 0 to 24 hours on Day 1
measure: Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1
timeFrame: 0 to 24 hours on Day 1
measure: Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%)
timeFrame: 0 to 24 hours on Day 22
measure: Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22
timeFrame: 0 to 24 hours on Day 22
measure: Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22
timeFrame: 0 to 24 hours on Day 22
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 Abnormalities in Physical Examination
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Change From Baseline in Systolic Blood Pressure (SBP) of Participants
timeFrame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
measure: Change From Baseline in Diastolic Blood Pressure (DBP) of Participants
timeFrame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
measure: Change From Baseline in Heart Rate of Participants
timeFrame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
measure: Change From Baseline in Respiratory Rate of Participants
timeFrame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
measure: Change From Baseline in Body Weight of Participants
timeFrame: Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to 30 days after last dose of study drug (up to 52 days)
measure: Number of Participants With Laboratory Abnormalities
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: Baseline, Safety follow up (Day 52)
Other outcomes:
Locations:
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute Weisberg Cancer Treatment Center
state: Michigan
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Durairaj C, Chakrabarti J, Ferrario C, Hirte HW, Babu S, Piha-Paul SA, Plotka A, Hoffman J, Shi H, Wang DD. The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors. Clin Pharmacokinet. 2021 Jul;60(7):921-930. doi: 10.1007/s40262-020-00983-y. Epub 2021 Mar 9.