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

NCT03562507 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: UMCC 2018.052HUM00142975
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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).

Conditions

Renal Cell Carcinoma, Metastatic

Keywords

ESK981

Outcome Measures

Primary Outcomes (1)

• 1. The Percentage of Patients That Respond to Treatment With the Combination of ESK981 Monotherapy and Nivolumab Therapy (Cohort B).

  The percentage of patients in Cohort B that achieve a complete response (CR) or partial response (PR). Response will be assessed by combined Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immune-related (ir)RECIST.

  Up to 24 months after last dose of study treatment

Secondary Outcomes (5)

• The Percentage of Patients That Respond to Treatment With ESK981 Monotherapy (Cohort A).

  Up to 24 months after last dose of study treatment, 5 month treatment duration on average, no CR or PR responses were recorded.

• Median Overall Survival Time

  Up to 24 months after last dose of study treatment

• Progression Free Survival Time

  Up to 24 months after last dose of study treatment

• Duration of Therapy

  Up to approximately 24 months after treatment start

• Duration of Response

  Up to 24 months after last dose of study treatment

Study Arms (2)

ESK981 Monotherapy

EXPERIMENTAL

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

Drug: ESK981

ESK981 and Nivolumab

EXPERIMENTAL

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

Drug: ESK981; Drug: Nivolumab

Interventions

ESK981 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 Monotherapy; ESK981 and Nivolumab

Nivolumab DRUG

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

ESK981 and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: ClinicalTrials.gov Cancer Center Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Ajjai Alva, MD

  Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There are 2 cohorts for accrual with Cohort A being accrued first. Cohort B will follow and will have 2 stages of accrual. Cohort A will accrue 11 patients to monotherapy treatment. Then Cohort B will begin accrual of 17 patients to the first stage and if the interim permits, the second stage will accrue an additional 19 patients.

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: June 19, 2018
• Study Start: April 11, 2019
• Primary Completion: October 18, 2022
• Study Completion: October 18, 2022
• Last Updated: May 20, 2024
• Results First Posted: May 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)