NCT07043608

Zanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases

A Phase II Study of Zanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases in Patients Previously Treated With Immune Checkpoint Inhibitors

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Kelly Fitzgerald, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-institution, phase 2 trial of zanzalintinib plus investigator-choice bone-strengthening agent in patients with metastatic renal cell carcinoma (RCC) with bone metastases whose disease has advanced on 1-3 prior lines of therapy, including at least one immune oncology-based (IO) therapy in the adjuvant or first-line metastatic setting.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate progression-free survival (PFS) at 12 months in participants with RECIST-measurable metastatic RCC and bone metastases at baseline, and who have been previously treated with contemporary IO-based therapy. SECONDARY OBJECTIVES: I. To determine the rate of skeletal-related events (SRE). II. To determine the rate of osteonecrosis of the jaw (ONJ). III. To determine the rate of systemic toxicity. IV. To determine median overall PFS. V. To determine median overall survival (OS) in participants. VI. To evaluate the objective response rate (ORR) in participants with measurable disease at baseline according to RECIST v 1.1. VII. To evaluate PFS at 24 months in patients with Response Evaluation Criteria in Solid Tumors (RECIST)-measurable disease (metastatic RCC and bone metastases) at baseline. EXPLORATORY OBJECTIVES: I. To evaluate the impact of treatment on osseous microenvironment including immune and metabolic microenvironment using Flow cytometry, bulk Ribonucleic acid sequencing (RNA-seq), Single-cell RNA sequencing (scRNA-seq), Immunohistochemistry (IHC), spatial genomic and/or proteomic profiling. II. Describe changes in quality of life (HRQoL) using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). OUTLINE: Participants will receive zanzalintinib and continue until criteria for removal from study are met. Investigator-choice bone-strengthening agent (BSA) will be administered at a standard dose/interval starting within 30 days of first study treatment. Non-investigational Radiation therapy (RT) for symptomatic metastases, including bone metastases, is allowed per investigator discretion. Participants may continue study treatment until unacceptable toxicity or demonstrated disease progression, or death whichever occurs first and followed for survival for up to 24 months.

Conditions

• Clear Cell Renal Cell Cancer (ccRCC)
• Clear Cell Renal Carcinoma
• Clear Cell Renal Cell Carcinoma Metastatic
• Clear Cell Renal Cancer
• Bone Metastases of a Malignant Tumor
• Clear Cell Renal Cell Carcinoma
• Bone, Metastatic Cancer
• Metastatic Cancer
• Metastatic Renal Cell Carcinoma
• Metastases to Bone

Interventions

Type	Name	Description
DRUG	Zanzalintinib	Given orally (PO)
DRUG	Investigator Choice of Bone Strengthening Agents (BSA)	One BSA will be chosen, at the discretion of the investigator and given intravenously (IV)
RADIATION	Non-Investigational Radiation Therapy (RT)	Non-investigational RT is permitted for symptomatic bone metastases.
PROCEDURE	Bone Scan	Undergo Bone Scan
PROCEDURE	Computerized tomography (CT) Scan	Undergo Imaging

Timeline

• Start date: 2025-09-30
• Primary completion: 2028-09-30
• Completion: 2029-09-30
• First posted: 2025-06-29
• Last updated: 2025-07-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study