A Phase Ib/II Study of Talazoparib and Axitinib in Metastatic Renal Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Talazoparib
- Conditions
- Kidney Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 23
- Locations
- 7
- Primary Endpoint
- Phase II: Objective Response Rate
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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)
- •Prior diagnosis of myelodysplastic syndrome (MDS) or diagnosis of other malignancy that requires anti-cancer directed therapy within the last 12 months. Exclusions include those cancers that are considered cured by local therapy (e.g. basal cell carcinoma, squamous cell carcinoma, ducal carcinoma in situ of breast, bladder of cervix) or other cancers that have low malignant potential and do not require systemic therapy (i.e. Gleason-grade \<6 prostate adenocarcinoma, borderline ovarian malignancy / low malignant potential).
- •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)
Arms & Interventions
Phase Ib, Dose Level 1
3-6 participants
Intervention: Talazoparib
Phase Ib, Dose Level 1
3-6 participants
Intervention: Axitinib
Phase Ib, Dose Level 2
3-6 participants
Intervention: Talazoparib
Phase Ib, Dose Level 2
3-6 participants
Intervention: Axitinib
Phase Ib, Dose Level 3
3-6 participants
Intervention: Talazoparib
Phase Ib, Dose Level 3
3-6 participants
Intervention: Axitinib
Phase II, Dose Expansion
Optimal Simon 2-stage Design (14 participants initially, if MTD is tolerated well then accrual will go up to 25 participants)
Intervention: Talazoparib
Phase II, Dose Expansion
Optimal Simon 2-stage Design (14 participants initially, if MTD is tolerated well then accrual will go up to 25 participants)
Intervention: Axitinib
Outcomes
Primary Outcomes
Phase II: Objective Response Rate
Time Frame: 2 years
Evaluate the efficacy as measured by objective response rate (ORR) of combination talazoparib and axitinib in previously treated metastatic clear cell RCC patients.
Phase Ib: Dose Limiting Toxicity
Time Frame: 28 days
Dose-limiting toxicity based on adverse events classified according to CTCAE v5.0 observed over 1 cycle of combination talazoparib and axitinib.
Phase Ib: Recommended dose of talazoparib in combination with standard-dose axitinib
Time Frame: 2 years
Identify the recommended dose of talazoparib in combination with standard-dose axitinib