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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04672460
• Other study ID #: C3441037
• Secondary ID: 2020-006101-35
• Status: Completed
• Phase: Phase 1
• Start date: December 21, 2020
• Est. completion date: July 22, 2022

Study information

• Verified date: August 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: July 22, 2022
• Est. primary completion date: February 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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) .

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Breast Cancer
• Colorectal Cancer
• Neoplasms
• NSCLC
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer
• Solid Tumors

Intervention

Drug:
• TALZENNA capsule
Current commercial talazoparib formulation 1 mg once daily given under fasting condition
• Talazoparib soft gel capsule
Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition
• Talazoparib soft gel capsule
Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Epworth Healthcare	East Melbourne	Victoria
Australia	Epworth Healthcare	East Melbourne
Australia	Epworth Healthcare (Epworth Freemasons Hospital)	East Melbourne	Victoria
Australia	Liverpool Cancer Therapy Centre	Liverpool	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Epworth Healthcare	Richmond	Victoria
Australia	Epworth Richmond Hospital (Epworth Healthcare)	Richmond	Victoria
United States	Montefiore Medical Center	Bronx	New York
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Mary Crowley Cancer Research - Medical City Hospital	Dallas	Texas
United States	California Cancer Associates for Research and Excellence, Inc (cCARE)	Encinitas	California
United States	Alliance for Multispecialty Research, LLC	Kansas City	Missouri
United States	Florida Cancer Specialists	Lake Mary	Florida
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	NYU Langone Hospital - Long Island Oncology	Mineola	New York
United States	Smilow Cancer Hospital at Yale New Haven	New Haven	Connecticut
United States	Smilow Cancer Hospital Phase 1 Unit	New Haven	Connecticut
United States	Yale-New Haven Hospital	New Haven	Connecticut
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	NYU Investigational Pharmacy	New York	New York
United States	NYU Langone Medical Center (Tisch Hospital)	New York	New York
United States	UPCI Investigational Drug Service	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Upmc Shadyside	Pittsburgh	Pennsylvania
United States	NEXT Oncology	San Antonio	Texas
United States	California Cancer Associates for Research and Excellence, Inc (cCARE)	San Marcos	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC24 of all talazoparib treatment	Area under the plasma concentration-time curve from time 0 to 24 hours	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Primary	Cmax of all talazoparib treatment	Maximum plasma concentration	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Secondary	Tmax of all talazoparib treatment	Time for Cmax	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Secondary	Ctrough of all talazoparib treatment	Predose plasma drug concentration	24 hours [On Day 27 for Period 1 and on Day 20 for Periods 2]
Secondary	CL/F of all talazoparib treatment	Apparent clearance after oral dose	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Secondary	AUClast of all talazoparib treatment	Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Secondary	Safety and tolerability of the proposed talazoparib soft gel capsule formulation	Incidence of AEs characterized by type, severity (graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment	Approximately 4 years

External Links

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