Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma

NCT ID: NCT03562507

Last Updated: 2024-05-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-11
• Study Completion Date: 2022-10-18

Brief Summary

The objective of the trial is to determine the clinical efficacy of ESK981 in combination with nivolumab therapy in patients with metastatic renal cell carcinoma (RCC).

Detailed Description

The study was terminated early due to changes in the RCC treatment landscape which limited the patient population. Due to this early termination no subjects were enrolled into Cohort B.

Conditions

Renal Cell Carcinoma, Metastatic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ESK981 Monotherapy

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Group Type: EXPERIMENTAL

ESK981

Intervention Type: DRUG

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

ESK981 and Nivolumab

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle

Group Type: EXPERIMENTAL

ESK981

Intervention Type: DRUG

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Nivolumab

Intervention Type: DRUG

480 mg/dose IV, Day 1 of each 28-day cycle

Interventions

ESK981

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Intervention Type: DRUG

Nivolumab

480 mg/dose IV, Day 1 of each 28-day cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologic diagnosis of renal cell carcinoma (any histology except medullary carcinoma or collecting duct carcinoma is acceptable) with radiologic or histologic evidence of metastatic disease.
• Prior treatment with up to one (and only one) anti-VEGF or VEGFR inhibitor (small molecule or antibody).
• Must have measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) criteria.
• Must be of age ≥ 18 years at time of informed consent.
• Ability to understand and the willingness to sign a written informed consent.
• Karnofsky Performance Status ≥60. (The Karnofsky Performance Status Scale is an assessment tool for functional impairment. It can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. In most serious illnesses, the lower the Karnofsky score, the worse the likelihood of survival.)
• Most recent systemic therapy or most recent radiation therapy ≥ 2 weeks of first study drug dose.
• Recovery to baseline or < Grade 1 CTCAE v.4.03 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to registration.
• Adequate organ and marrow function

Exclusion Criteria

• Prior treatment for metastatic disease with >1 anti-VEGF/VEGFR inhibitor.
• Prior treatment with anti-PD/PD-L1/CTLA4/IDO antibody (for Cohort B patients only) or ESK981 (for Cohort A and Cohort B patients).
• Prior mTOR inhibitors or glutaminase inhibitors are allowed.
• Untreated brain metastases or spinal cord compression.
• Uncontrolled hypertension defined as blood pressure >150/90 despite at least 2 anti-hypertensive medication(s) as assessed by 2 blood pressure readings taken at least 1 hour apart during screening.
• Major surgical procedure or significant traumatic injury within 6 weeks prior to study registration (> 6 weeks prior to registration is permitted as long as they have fully recovered from any such procedure).
• History of another primary malignancy except for: malignancy treated with curative intent and no known active disease for ≥2 years, adequately treated non-melanoma skin cancer without current evidence of active disease, adequately treated carcinoma in situ without current evidence of active disease, Gleason ≤6 prostate cancer.
• Angina, myocardial infarction symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous angioplasty or coronary arterial bypass surgery within the past 3 months.
• History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g. through surgical resection or repair).
• The patient has known hypersensitivity to gelatin or lactose monohydrate.
• The patient has received any investigational drug within 28 days prior to registration or 5 half-lives of the investigational drug, whichever is shorter.
• History of bleeding disorders (e.g. pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ≤ 6 weeks before Cycle 1 Day1.
• The patient is on a chronic daily medication known to be a severe or moderate inhibitor or inducer by Micromedex of CYP1A2, CYP2C8, or CYP3A4 at registration.
• Systemic corticosteroids greater than the equivalent of 10 mg of prednisone or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate) and any other medications that could potentially impact the efficacy or safety of the study as judged by the treating investigator are NOT permitted from time of registration to subjects completing protocol therapy unless clinically indicated to manage adverse events or life threatening or serious conditions as determined by the treating investigator.
• Have any condition that, in the opinion of the investigator, would compromise the ability of the subject to meet or perform study requirements.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajjai Alva, MD

Role: PRINCIPAL_INVESTIGATOR

Rogel Cancer Center

Locations

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HUM00142975

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2018.052

Identifier Type: -

Identifier Source: org_study_id