NCT03905889

A Study of Abemaciclib in Combination With Sunitinib in Metastatic Renal Cell Carcinoma

Targeting PIM1 and CDK4/6 Kinases in Renal Cell Carcinoma (PICKRCC): A Phase Ib Study of Abemaciclib (VerzenioTM) in Combination With Sunitinib in Metastatic Renal Cell Carcinoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Brown University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the safety, tolerability, and maximal tolerated dose (MTD) of the combination of Abemaciclib and Sunitinib administered orally in patients with advanced and metastatic renal cell carcinoma. This study consists of two parts: Dose Escalation and Dose Expansion. During the dose escalation phase, participants will be sequentially enrolled in a standard 3 x 3 dose escalation study design to receive oral Abemaciclib in Combination with Sunitinib. The purpose of this dose escalation is to determine the maximal tolerated dose based on assessment of any dose limiting toxicity. The Dose Expansion Phase will enroll additional participants at the established maximal tolerated dose to further evaluate safety, tolerability, as well as the pharmacokinetics and pharmacodynamics of this combination drug regimen.

Detailed description

Renal cell carcinoma (RCC) accounted for about 64, 000 new cancer diagnoses in the USA in 2018. Up to 30% of those diagnoses will be patients with metastatic disease. Additionally, up to 50% of patients who undergo partial or radical nephrectomy will develop metastatic disease.. There is no cure for metastatic RCC, thus, metastatic RCC represents a significant cancer burden. Numerous directed therapies are available to improve overall survival but these do not result in durable complete responses. However, recent pre-clinical studies of RCC have demonstrated that Abemaciclib, a CDK4/6 and PIM1 kinase inhibitor, induces rapid, dramatic, and sustained tumor regression when used in combination with Sunitinib. Our objectives for this study are as follows: Primary Objectives: * Determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the combination of Abemaciclib with Sunitinib for patients with metastatic renal cell carcinoma. Additionally, determine pharmacokinetics (serum trough levels) of Abemaciclib and Sunitinib at steady state. * Continued safety assessment of the combination of Abemaciclib and Sunitinib at the established maximum tolerated dose (i.e. the recommended Phase II dose) Secondary Objectives: Determine any anti-tumor activity in the dose expansion phase of the study. Tumor related activity will be assessed by: * Length of progression free survival * Disease response rate * Time to disease response * Disease control rate * Duration of response * Overall survival and progression free survival

Conditions

• Renal Cell Carcinoma Metastatic

Interventions

Type	Name	Description
DRUG	Abemaciclib	Subjects will by given oral Abemaciclib every 12 hours for 14 days followed by 7 days off (i.e. a 21 day cycle). The initial dose will be 100 mg (Dose level 1) followed by 150 mg (Dose Level 2) depending on tolerability and toxicity assessment of the combination of medications. If at Dose Level 1 subjects cannot tolerate the combination of medications, the Abemaciclib would not be increased, and the dose will remain stable at 100 mg (Dose Level -1).
DRUG	Sunitinib	Subjects will take oral Sunitinib daily for the 21-day cycle. Dosing will be at 50 mg for both Dose Levels 1 and 2. If the combination of the 2 medications is not tolerated by Subjects at Dose Levels 1 a lower dose of Sunitinib (37.5 mg) will be given (Dose Level -1).

Timeline

• Start date: 2019-06-05
• Primary completion: 2022-03-08
• Completion: 2022-03-08
• First posted: 2019-04-05
• Last updated: 2024-06-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study