- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03562507
Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma (ERICA)
September 18, 2023 updated by: University of Michigan Rogel Cancer Center
ERICA: Phase 2 Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma
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).
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Comprehensive Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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
|
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
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Experimental: 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 |
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
480 mg/dose IV, Day 1 of each 28-day cycle
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1. The percentage of patients that respond to treatment with the combination of ESK981 monotherapy and nivolumab therapy (Cohort B).
Time Frame: Up to 24 months after last dose of study treatment
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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.
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Up to 24 months after last dose of study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
2. The percentage of patients that respond to treatment with ESK981 monotherapy (Cohort A).
Time Frame: Up to 24 months after last dose of study treatment
|
The percentage of patients in Cohort A that achieve a complete response (CR) or partial response (PR).
Response will be assessed by RECIST v1.1.
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Up to 24 months after last dose of study treatment
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Median overall survival time
Time Frame: Up to 24 months after last dose of study treatment
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Overall survival time measured from start of treatment until up to 24 months after the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).
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Up to 24 months after last dose of study treatment
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Progression free survival time
Time Frame: Up to 24 months after last dose of study treatment
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Measured from start of treatment to time of progression or death, or up to 24 months after the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).
Disease progression will be assessed by RECIST v1.1 in Cohort A and by combined RECIST v1.1/irRECIST in Cohort B.
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Up to 24 months after last dose of study treatment
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Duration of therapy
Time Frame: Up to approximately 24 months after treatment start
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Measured from the first to the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).
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Up to approximately 24 months after treatment start
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Duration of response
Time Frame: Up to 24 months after last dose of study treatment
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Measured from the time of complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Response will be assessed by RECIST v1.1 (Cohort A) and by combined RECIST v1.1/irRECIST (Cohort B).
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Up to 24 months after last dose of study treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Ajjai Alva, MD, Rogel Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 11, 2019
Primary Completion (Actual)
October 18, 2022
Study Completion (Actual)
October 18, 2022
Study Registration Dates
First Submitted
June 8, 2018
First Submitted That Met QC Criteria
June 8, 2018
First Posted (Actual)
June 19, 2018
Study Record Updates
Last Update Posted (Actual)
September 21, 2023
Last Update Submitted That Met QC Criteria
September 18, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Carcinoma, Renal Cell
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- UMCC 2018.052
- HUM00142975 (Other Identifier: University of Michigan)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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