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

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT04672460
Collaborator
(none)
74
30
2
19
2.5
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: TALZENNA capsule
  • Drug: Talazoparib soft gel capsule
  • Drug: Talazoparib soft gel capsule
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
74 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 21, 2020
Actual Primary Completion Date :
Feb 4, 2022
Actual Study Completion Date :
Jul 22, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sequence 1

Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.

Drug: TALZENNA capsule
Current commercial talazoparib formulation 1 mg once daily given under fasting condition

Drug: Talazoparib soft gel capsule
Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition

Drug: Talazoparib soft gel capsule
Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition

Experimental: Sequence 2

Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.

Drug: TALZENNA capsule
Current commercial talazoparib formulation 1 mg once daily given under fasting condition

Drug: Talazoparib soft gel capsule
Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition

Drug: Talazoparib soft gel capsule
Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition

Outcome Measures

Primary Outcome Measures

  1. AUC24 of all talazoparib treatment [24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]]

    Area under the plasma concentration-time curve from time 0 to 24 hours

  2. Cmax of all talazoparib treatment [24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]]

    Maximum plasma concentration

Secondary Outcome Measures

  1. Tmax of all talazoparib treatment [24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]]

    Time for Cmax

  2. Ctrough of all talazoparib treatment [24 hours [On Day 27 for Period 1 and on Day 20 for Periods 2]]

    Predose plasma drug concentration

  3. CL/F of all talazoparib treatment [24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]]

    Apparent clearance after oral dose

  4. AUClast of all talazoparib treatment [24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]]

    Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)

  5. Safety and tolerability of the proposed talazoparib soft gel capsule formulation [Approximately 4 years]

    Incidence of AEs characterized by type, severity (graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

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.

  1. ECOG performance score of 0-1.

  2. Adequate bone marrow function:

  • ANC ≥1500 cells/mm3

  • Platelets ≥100,000 cells/mm3

  • Hemoglobin ≥10.0 g/dL

  1. 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) .

Contacts and Locations

Locations

Site City State Country Postal Code
1 California Cancer Associates for Research and Excellence, Inc (cCARE) Encinitas California United States 92024
2 Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute Los Angeles California United States 90048
3 Cedars-Sinai Medical Center Los Angeles California United States 90048
4 California Cancer Associates for Research and Excellence, Inc (cCARE) San Marcos California United States 92069
5 Smilow Cancer Hospital at Yale New Haven New Haven Connecticut United States 06510
6 Yale-New Haven Hospital New Haven Connecticut United States 06510
7 Smilow Cancer Hospital Phase 1 Unit New Haven Connecticut United States 06511
8 Florida Cancer Specialists Lake Mary Florida United States 32746
9 Alliance for Multispecialty Research, LLC Kansas City Missouri United States 64114
10 Montefiore Medical Center Bronx New York United States 10461
11 NYU Langone Hospital - Long Island Oncology Mineola New York United States 11501
12 NYU Langone Hospital - Long Island Mineola New York United States 11501
13 Laura & Isaac Perlmutter Cancer Center at NYU Langone Health New York New York United States 10016
14 NYU Investigational Pharmacy New York New York United States 10016
15 NYU Langone Medical Center (Tisch Hospital) New York New York United States 10016
16 University of Cincinnati Medical Center Cincinnati Ohio United States 45219
17 University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
18 UPCI Investigational Drug Service Pittsburgh Pennsylvania United States 15232
19 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
20 Upmc Shadyside Pittsburgh Pennsylvania United States 15232
21 Mary Crowley Cancer Research - Medical City Hospital Dallas Texas United States 75230
22 NEXT Oncology San Antonio Texas United States 78229
23 Liverpool Cancer Therapy Centre Liverpool New South Wales Australia 2170
24 Liverpool Hospital Liverpool New South Wales Australia 2170
25 Monash Health Clayton Victoria Australia 3168
26 Epworth Healthcare (Epworth Freemasons Hospital) East Melbourne Victoria Australia 3002
27 Epworth Healthcare East Melbourne Victoria Australia 3002
28 Epworth Healthcare Richmond Victoria Australia 3121
29 Epworth Richmond Hospital (Epworth Healthcare) Richmond Victoria Australia 3121
30 Epworth Healthcare East Melbourne Australia 3002

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT04672460
Other Study ID Numbers:
  • C3441037
  • 2020-006101-35
First Posted:
Dec 17, 2020
Last Update Posted:
Aug 5, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 5, 2022