Clinical trial NCT04672460: A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors
Official title: A PHASE 1, OPEN LABEL, CROSSOVER STUDY TO ESTABLISH BIOEQUIVALENCE BETWEEN THE PROPOSED SOFT GEL TALAZOPARIB CAPSULE FORMULATION AND THE CURRENT TALAZOPARIB COMMERCIAL FORMULATION AND TO ESTIMATE THE FOOD EFFECT ON PHARMACOKINETICS OF THE PROPOSED TALAZOPARIB SOFT GEL CAPSULE FORMULATION IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Solid Tumors
Ovarian Cancer
Breast Cancer
Prostate Cancer
NSCLC
Pancreatic Cancer
Colorectal Cancer
Keywords: PARP inhibitor
Talazoparib
Talzenna
BRCA mutation
ATM mutation
Pharmacokinetics
Bioequivalence
Bioavailability
Food effect
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be randomly assigned to 1 of 2 sequences to receive Treatment A, B and C in different order as shown below. The first 2 periods will be for BE assessment, with the first period being 28 days and the following periods being 21 days. Period 3 will be a 21 day period to evaluate the food effect on the PK of the proposed talazoparib soft gel capsule formulation that will be included in the fixed sequence after the 2 BE assessment periods (for participants who can tolerate one high-fat/high-calorie meal). Participants must have received 21 consecutive days of continuous 1mg QD drug administration to be considered as completers of a treatment period, before moving on to the next scheduled treatment.
Primary purpose: TREATMENT

Brief summary: This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple dosing under fasting conditions in participants with advanced solid tumors. In addition, the effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be evaluated in fixed sequence after the 2 BE assessment periods.


Eligibility criteria: Inclusion Criteria

1. Histological diagnosis of recurrent, locally advanced or metastatic solid tumor that is not amenable for treatment with curative intent.

   * Solid tumors with known or likely pathogenic germline or somatic tumor gene defect (eg, one or more BRCA1 or BRCA2 gene defect except for ovarian cancer) that would benefit from PARPi therapy per current approvals for the tumor indication or supported by strong scientific evidence.
   * Received at least 1 prior SOC regimen, if it exists, as appropriate for the respective tumor type unless deemed unsuitable or declined these therapies; ovarian cancer participants must have at least 1 prior cytotoxic chemotherapy regimen, including at least 1 course of platinum-based therapy. Participants must not have had disease progression within 6 months of initiation of platinum containing regimen.
2. ECOG performance score of 0-1.
3. Adequate bone marrow function:

   * ANC ≥1500 cells/mm3
   * Platelets ≥100,000 cells/mm3
   * Hemoglobin ≥10.0 g/dL
4. Adequate organ functions:

   * CLCR ≥60 mL/min and no documented CLCR \<60 mL/min and no change in CLCR \>25% in the past 4 weeks
   * AST and ALT ≤2.5 × ULN; if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤5 × ULN;
   * Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert's syndrome);

Exclusion Criteria

1. For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
2. Toxicities from previous anti-cancer therapies must be resolved to NCI CTCAE \<Grade 2, except for alopecia, sensory neuropathies ≤Grade 2, or other Grade ≤2 AEs not constituting a safety risk, based on investigator's judgment, are acceptable.
3. Diagnosed with MDS or AML.
4. Active infection requiring systemic therapy within 2 weeks of enrollment.
5. Any condition in which active bleeding or pathological conditions may carry a high risk of bleeding (eg, known bleeding disorder, coagulopathy or tumor involvement with major vessels).
6. Known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment. Asymptomatic brain metastases currently not undergoing treatment are allowed.
7. Known history of testing positive for HIV, AIDS, positive HBV surface antigen, positive HCV RNA, or positive COVID-19 viral test. Asymptomatic patients with no active infection detected but positive antibody tests, indicating past infection, are allowed.
8. Current or anticipated use of P-gp inhibitors, BCRP inhibitors, and P-gp inducers within 2 weeks or 5 half-lives prior to randomization (whichever is longer) .

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fasted Conditions
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fasted Conditions
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fed Conditions
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fed Conditions
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
Secondary outcomes:
measure: Apparent Clearance After Oral Dose (CL/F) of Talazoparib After Multiple Dosing
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Time of Observed Maximum Plasma Concentration (Tmax) of Talazoparib After Multiple Dosing
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Area Under the Plasma Concentration-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of Talazoparib After Multiple Dosing
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Predose Concentration During Multiple Dosing (Ctrough) of Talazoparib After Multiple Dosing
timeFrame: Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2, predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities)
timeFrame: Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related)
timeFrame: Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence, Inc (cCARE)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research and Excellence, Inc (cCARE)
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital Phase 1 Unit
state: Connecticut
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island Oncology
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: NYU Investigational Pharmacy
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center (Tisch Hospital)
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: West Chester
country: United States
facility: West Chester Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: UPCI Investigational Drug Service
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Upmc Shadyside
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Research - Medical City Hospital
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Liverpool
country: Australia
facility: Liverpool Cancer Therapy Centre
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: East Melbourne
country: Australia
facility: Epworth Healthcare (Epworth Freemasons Hospital)
state: Victoria
city: East Melbourne
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Richmond
country: Australia
facility: Epworth Richmond Hospital (Epworth Healthcare)
state: Victoria
city: East Melbourne
country: Australia
facility: Epworth Healthcare
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: