Clinical Trials /

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

NCT03562507

Description:

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.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma
  • Official Title: ERICA: Phase 2 Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2018.052
  • SECONDARY ID: HUM00142975
  • NCT ID: NCT03562507

Conditions

  • Renal Cell Carcinoma, Metastatic

Interventions

DrugSynonymsArms
ESK981ESK981 Monotherapy
NivolumabESK981 and Nivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ESK981 MonotherapyExperimentalESK981: 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
ESK981 and NivolumabExperimentalESK981: 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
  • Nivolumab

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 or ESK981.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description: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.
Measure:Median overall survival time
Time Frame:Up to 24 months after last dose of study treatment
Safety Issue:
Description: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).
Measure:Progression free survival time
Time Frame:Up to 24 months after last dose of study treatment
Safety Issue:
Description: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.
Measure:Duration of therapy
Time Frame:Up to approximately 24 months after treatment start
Safety Issue:
Description: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).
Measure:Duration of response
Time Frame:Up to 24 months after last dose of study treatment
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Trial Keywords

  • ESK981

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