Cabozantinib and Pembrolizumab for Advanced Metastatic Melanoma

Phase 1

Terminated

Brief Summary: The study aims to evaluate the safety and preliminary efficacy of the combination of cabozantinib and pembrolizumab in advanced melanoma

Detailed Description: This is an open-label, Phase 1b/2 trial for adults with advanced melanoma. The objective of the Phase 1b portion of the study is to establish the recommended Phase 2 dose of cabozantinib in combination with pembrolizumab in patients with unresectable melanoma and assess the safety and tolerability of the combined treatments. The objective of the Phase 2 portion of the study is to evaluate the preliminary efficacy of the established dose of cabozantinib in combination with pembrolizumab as measured by best overall response rate (ORR) (complete response \[CR\] + partial response \[PR\]) with the combination of agents in patients with unresectable stage III or stage IV melanoma.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Cabozantinib and pembrolizumab	Cabozantinib	Cabozantinib will be administered in the tablet form, at three dose levels: 40, 20 and 60 mg per day. Pembrolizumab will be administered as an intravenous infusion at a fixed dose of 200 mg once every 3 weeks.
Cabozantinib and pembrolizumab	Pembrolizumab	Cabozantinib will be administered in the tablet form, at three dose levels: 40, 20 and 60 mg per day. Pembrolizumab will be administered as an intravenous infusion at a fixed dose of 200 mg once every 3 weeks.

Primary Outcome Measures

Name	Time	Method
Phase I: Number of Participants With a Dose Limiting Toxicity (DLT) Using CTCAE, Version 4.03	Up to 21 days	All adverse events (AEs) will be considered in DLT assessment unless an event is clearly unrelated to trial treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 will be used.
Phase II: Overall Response Rate	Initiation of treatment up to 2 years	The overall response rate (ORR) is the percentage of patients with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). A complete response (CR) is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm, and partial response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions.

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate	Initiation of treatment up to 2 years	The disease control rate (DCR) is the percentage of patients with a complete response (CR), partial response (PR) or stable disease (SD) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). A complete response (CR) is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm, partial response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions, and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Progression-Free Survival	Initiation of treatment up to 2 years	Progression-free survival (PFS) is defined as the time from study treatment initiation to the date of first documentation of disease progression or death due to any cause. Otherwise, patients were censored at date of last radiographic assessment.
Overall Survival at 2 Years	Initiation of treatment up to 2 years	Overall survival (OS) is defined as the time from study treatment initiation to death due to any cause. Patients still alive were censored at the last date known to be alive. Cumulative OS was descriptively summarized over time with the Kaplan-Meier method. The landmark estimate at 2 years and associated 95% confidence interval is reported.

Locations (1): University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States