NCT05038839

Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors

A Phase I Study of Cabozantinib and Pamiparib to Evaluate Triple Inhibition of PARP, VEGFR and c-MET in Advanced Homologous Recombination Deficient Malignancies

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial finds the best dose and side effects of cabozantinib and pamiparib in treating patients with solid tumors that have spread to other places in the body (advanced) or does not respond to treatment (refractory). Cabozantinib and pamiparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD) or maximum administered dose (MAD) and dose-limiting toxic effects (DLTs) of cabozantinib and pamiparib. II. To define the safety profiles of cabozantinib and pamiparib. SECONDARY OBJECTIVES: I. To perform plasma pharmacokinetic analyses of cabozantinib and pamiparib interaction. II. To evaluate patient reported outcomes (PRO). III. To evaluate pre-identified mutations in circulating free deoxyribonucleic acid (DNA) (cfDNA) by next generation sequencing (NGS). IV. To estimate complete responses (CRs), partial responses (PRs), stable disease \>= 6 months (SD \>= 6months), progression free survival (PFS) and overall survival (OS). V. To relate changes in phosphorylated AKT (pAKT), phosphorylated ERK2 (pERK2), phosphorylated c-MET (pc-MET), phosphorylated PARP1 (PARP1-pY907), phosphorylated histone H2A variant H2AX (gamma-H2AX) and RAD51 in tumor specimens with antitumor efficacy. VI. To relate cancer-associated mutations at baseline with antitumor efficacy. VII. To explore potential biomarkers of acquired resistance by comparing molecular signatures at baseline with those at time of relapse in patients in whom SD \>= 6 months/CR/PR or a mixed response are documented, by next-generation deep sequencing or more sophisticated techniques. OUTLINE: This is a dose-escalation study. Patients receive cabozantinib orally (PO) once daily (QD) and pamiparib PO twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 6 months.

Conditions

• Advanced Malignant Solid Neoplasm
• Refractory Malignant Solid Neoplasm

Interventions

Type	Name	Description
DRUG	Cabozantinib	Given PO
DRUG	Pamiparib	Given PO

Timeline

• Start date: 2022-02-09
• Primary completion: 2026-06-03
• Completion: 2026-06-03
• First posted: 2021-09-09
• Last updated: 2025-11-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study