Talazoparib and Axitinib for People With Previously Treated Advanced Kidney Cancer
A Phase Ib/II Study of Talazoparib and Axitinib in Metastatic Renal Cell Carcinoma
1 other identifier
interventional
23
1 country
7
Brief Summary
Researchers are doing this study to find out if the combination of the drugs axitinib and talazoparib is a safe and effective treatment for people with your previously treated advanced kidney cancer. Researchers will look for the highest dose of talazoparib that causes few or mild side effects when given in combination with a standard dose of axitinib.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2020
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 6, 2020
CompletedStudy Start
First participant enrolled
April 6, 2020
CompletedFirst Posted
Study publicly available on registry
April 8, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 23, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 23, 2025
CompletedMay 28, 2025
May 1, 2025
5.1 years
April 6, 2020
May 23, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase Ib: Recommended dose of talazoparib in combination with standard-dose axitinib
Identify the recommended dose of talazoparib in combination with standard-dose axitinib
2 years
Phase Ib: Dose Limiting Toxicity
Dose-limiting toxicity based on adverse events classified according to CTCAE v5.0 observed over 1 cycle of combination talazoparib and axitinib.
28 days
Phase II: Objective Response Rate
Evaluate the efficacy as measured by objective response rate (ORR) of combination talazoparib and axitinib in previously treated metastatic clear cell RCC patients.
2 years
Study Arms (4)
Phase Ib, Dose Level 1
EXPERIMENTAL3-6 participants
Phase Ib, Dose Level 2
EXPERIMENTAL3-6 participants
Phase Ib, Dose Level 3
EXPERIMENTAL3-6 participants
Phase II, Dose Expansion
EXPERIMENTALOptimal Simon 2-stage Design (14 participants initially, if MTD is tolerated well then accrual will go up to 25 participants)
Interventions
Dose Level 1: 0.5 mg PO daily Dose Level 2: 0.75 mg PO daily Dose Level 3: 1 mg PO daily Phase II: MTD to be determined.
5 mg PO BID
Eligibility Criteria
You may qualify if:
- Biopsy proven metastatic or unresectable renal cell carcinoma with clear cell component
- Prior treatment with at least 1 VEGFR TKI and 1 PD-1/PD-L1 immune checkpoint inhibitor (ICI).Combination VEGFR TKI plus ICI will be counted as 1 line of therapy. During the dose escalation portion of the study prior TKI exposure is not required.
- Dose escalation portion: No maximum prior lines of therapy. Dose expansion portion: maximum of two prior lines of therapy
- Adequate Hematologic Function
- Absolute Neutrophil Count ≥ 1.5 x 109 / L
- Platelet Count ≥ 100 x 10\^9 / L
- Hemoglobin ≥ 9 g/dL
- No transfusion of packed red blood cells or platelets within 21 days of Cycle 1 Day 1
- Adequate Renal Function ≥ 60 ml/min according to the Cockcroft-Gault formula
- ° Patients with moderate renal impairment (creatinine clearance 30-59 ml/min by Cockcroft-Gault) may be eligible in the phase II dose expansion
- Adequate Hepatic Function including:
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- AST ≤ 3 x upper limit of normal (ULN) without liver metastasis
- ALT ≤ 3 x upper limit of normal (ULN) without liver metastasis
- AST or ALT ≤ 5 x upper limit of normal (ULN) for patients with liver metastasis
- +14 more criteria
You may not qualify if:
- Prior treatment with talazoparib or other agents which target PARP
- Prior treatment with axitinib. Other VEGFR TKIs are permissible.
- Patients \< 18 years old
- Patients who are pregnant or breast-feeding. Fertile patients who are unwilling or unable to use two methods of contraception (at least one of which considered highly effective) for duration of study and after study (7 months after last dose of the study treatment for women, and 4 months for men)
- Treatment with anti-cancer therapies within 21 days or five half-lives, whichever shorter, of start date, including monoclonal antibody, cytotoxic therapy, or another investigational agent.
- Significant vascular disease (i.e. aortic aneurysm requiring surgical repair, recent arterial thrombosis) within 6 months prior to first dose of therapy.
- Ejection Fraction (EF) ≤50% by echocardiogram (ECHO). Multi-gated acquisition scan (MUGA) should be obtained to estimate EF if quality of ECHO is insufficient.
- Uncontrolled hypertension defined as systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥ 100 mmHg despite anti-HTN therapy.
- Evidence of bleeding diathesis or significant unexplained coagulopathy (i.e. absent of anticoagulation)
- Clinical signs or symptoms of gastrointestinal obstruction requirement parenteral hydration, parenteral nutrition, or feeding tube.
- Uncontrolled effusion management (pleural effusion, pericardial effusion, or ascites) which requires recurrent drainage procedures.
- Active infection requiring parenteral antibiotic therapy.
- History of either positive HCV RNA viral load or anti-HCV antibody screening detectable; HBV infection with HBV surface antigen detection and/or positive HBV DNA viral load.
- Known hypersensitivity to talazoparib or axitinib, or any component in formulations.
- Severe acute or chronic medical conditions which may significantly increase the risk of study participants, per treating investigator's discretion.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553, United States
Related Publications (1)
Kotecha RR, Doshi SD, Knezevic A, Jacobi R, Woo HJ, Aggen DH, McHugh DJ, Shah NJ, Carlo MI, Keegan NM, Gayadin Y, Chaim J, Donoghue MTA, Iyer G, Lee CH, Feldman DR, Motzer RJ, Voss MH. A Phase 1b/2 Study of Talazoparib and Axitinib in Patients with Advanced Clear-cell Renal Cell Carcinoma. Eur Urol Oncol. 2025 Aug;8(4):866-870. doi: 10.1016/j.euo.2025.03.010. Epub 2025 Mar 29.
PMID: 40158923BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ritesh Kotecha, MD
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 6, 2020
First Posted
April 8, 2020
Study Start
April 6, 2020
Primary Completion
May 23, 2025
Study Completion
May 23, 2025
Last Updated
May 28, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.