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

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ClinicalTrials.gov Identifier: NCT03562507
Recruitment Status : Active, not recruiting
First Posted : June 19, 2018
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma, Metastatic Drug: ESK981 Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ERICA: Phase 2 Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma
Actual Study Start Date : April 11, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023


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
Drug: 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

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

Drug: 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

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




Primary Outcome Measures :
  1. 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 ]
    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.


Secondary Outcome Measures :
  1. 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.

  2. Median overall survival time [ Time Frame: Up to 24 months after last dose of study treatment ]
    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).

  3. Progression free survival time [ Time Frame: Up to 24 months after last dose of study treatment ]
    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.

  4. Duration of therapy [ Time Frame: Up to approximately 24 months after treatment start ]
    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).

  5. Duration of response [ Time Frame: Up to 24 months after last dose of study treatment ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03562507


Locations
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United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Ajjai Alva, MD Rogel Cancer Center
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT03562507    
Other Study ID Numbers: UMCC 2018.052
HUM00142975 ( Other Identifier: University of Michigan )
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Michigan Rogel Cancer Center:
ESK981
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action