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Advanced Solid TumorsPhase 1NCT04672460

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

A Phase 1 study testing TALZENNA capsule and Talazoparib soft gel capsule in people with Advanced Solid Tumors and Solid Tumors, run by Pfizer at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
TALZENNA capsule and Talazoparib soft gel capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
73 participants
Where
31 sitesin 2 countries
Study dates
21 Dec 2020to 22 Jul 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • ECOG performance score of 0-1.
  • Adequate bone marrow function:
  • ANC ≥1500 cells/mm3
Show all 12Show fewer
  • Platelets ≥100,000 cells/mm3
  • Hemoglobin ≥10.0 g/dL
  • 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);

Who cannot join

  • For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
  • 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.
  • Diagnosed with MDS or AML.
  • Active infection requiring systemic therapy within 2 weeks of enrollment.
  • 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).
  • Known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment. Asymptomatic brain metastases currently not undergoing treatment are allowed.
  • 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.
  • 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) .

Trial locations and contacts

31 sites in 2 countries.

31 sites in 2 countries

United States23 sites

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Mary Crowley Cancer Research - Medical City Hospital

    Dallas, Texas, 75230

  • California Cancer Associates for Research and Excellence, Inc (cCARE)

    Encinitas, California, 92024

  • Alliance for Multispecialty Research, LLC

    Kansas City, Missouri, 64114

  • Florida Cancer Specialists

    Lake Mary, Florida, 32746

  • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

    Los Angeles, California, 90048

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • NYU Langone Hospital - Long Island Oncology

    Mineola, New York, 11501

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

  • Smilow Cancer Hospital at Yale New Haven

    New Haven, Connecticut, 06510

  • Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Smilow Cancer Hospital Phase 1 Unit

    New Haven, Connecticut, 06511

  • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

    New York, New York, 10016

  • NYU Investigational Pharmacy

    New York, New York, 10016

  • NYU Langone Medical Center (Tisch Hospital)

    New York, New York, 10016

  • UPCI Investigational Drug Service

    Pittsburgh, Pennsylvania, 15232

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Upmc Shadyside

    Pittsburgh, Pennsylvania, 15232

  • NEXT Oncology

    San Antonio, Texas, 78229

  • California Cancer Associates for Research and Excellence, Inc (cCARE)

    San Marcos, California, 92069

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • West Chester Hospital

    West Chester, Ohio, 45069

Other trials in United States

Australia8 sites

  • Monash Health

    Clayton, Victoria, 3168

  • Epworth Healthcare (Epworth Freemasons Hospital)

    East Melbourne, Victoria, 3002

  • Epworth Healthcare

    East Melbourne, Victoria, 3002

  • Epworth Healthcare

    East Melbourne, 3002

  • Liverpool Cancer Therapy Centre

    Liverpool, New South Wales, 2170

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Epworth Healthcare

    Richmond, Victoria, 3121

  • Epworth Richmond Hospital (Epworth Healthcare)

    Richmond, Victoria, 3121

Other trials in Australia

About this study

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

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.

Being tested
TALZENNA capsule, Talazoparib soft gel capsule
Keywords
PARP inhibitor, Talazoparib, Talzenna, BRCA mutation, ATM mutation, Pharmacokinetics, Bioequivalence, Bioavailability, Food effect
Medical subject headings
Ovarian Neoplasms, Breast Neoplasms, Prostatic Neoplasms, Pancreatic Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TALZENNA capsuleDrug

    Current commercial talazoparib formulation 1 mg once daily given under fasting condition

  • Talazoparib soft gel capsuleDrug

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

  • Talazoparib soft gel capsuleDrug

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

Study groups in NCT04672460
Study groupRoleWhat they receive
Sequence 1ExperimentalParticipants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.
Receives: Drug: TALZENNA capsule; Drug: Talazoparib soft gel capsule
Sequence 2ExperimentalParticipants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.
Receives: Drug: TALZENNA capsule; Drug: Talazoparib soft gel capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fasted Conditions

    AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

    Measured: 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.

  2. Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fasted Conditions

    Cmax was the maximum observed plasma concentration and was directly observed from data. The geometric coefficient of variation was expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

    Measured: 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.

  3. Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fed Conditions

    AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

    Measured: 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.

  4. Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fed Conditions

    Cmax was the maximum observed plasma concentration and was directly observed from data. The geometric coefficient of variation was expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

    Measured: 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 (6)

  1. Apparent Clearance After Oral Dose (CL/F) of Talazoparib After Multiple Dosing

    Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. The geometric coefficient of variation is expressed in percentage.

    Measured: 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.

  2. Time of Observed Maximum Plasma Concentration (Tmax) of Talazoparib After Multiple Dosing

    Tmax was defined as time to reach maximum observed plasma concentration.

    Measured: 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.

  3. Area Under the Plasma Concentration-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of Talazoparib After Multiple Dosing

    AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage.

    Measured: 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.

  4. Predose Concentration During Multiple Dosing (Ctrough) of Talazoparib After Multiple Dosing

    Ctrough was the pre-dose concentration during multiple dosing and was directly observed from data. The geometric coefficient of variation is expressed in percentage.

    Measured: 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.

  5. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities)

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.

    Measured: Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)

  6. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Treatment Related)

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.

    Measured: Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2020
  2. Study start21 Dec 2020
  3. Primary completion4 Feb 2022
  4. Study completion22 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
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.
Masking
None (open label)
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04672460
Sponsor's protocol ID
C3441037
Other IDs
2020-006101-35
Status last verified
Jun 2024
First submitted
13 Nov 2020
Last updated
25 Sep 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Wang D, Guo CC, Gao X, Wang Y, Yu Y, Plotka A, Elmeliegy M, Shi H, Johnson S, DeAnnuntis L, Hoffman J. Talazoparib Formulation Bridging in Cancer Patients-Challenges and the Critical Role of Model-Informed Drug Development in Approval Despite Failed Bioequivalence. CPT Pharmacometrics Syst Pharmacol. 2026 Jan;15(1):e70157. doi: 10.1002/psp4.70157. Epub 2025 Dec 11.

    PubMed 41379622

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TALZENNA capsule and Talazoparib soft gel capsule in people with Advanced Solid Tumors and Solid Tumors, run by Pfizer at 31 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fasted Conditions (time frame: 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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04672460, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2024.

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