Actively Recruiting

Phase 2
Age: 18Years +
All Genders
ID05361720

Optimal Treatment by Invoking Biologic Clusters in Renal Cell Carcinoma (OPTIC RCC)

Led by Vanderbilt-Ingram Cancer Center · Updated on 2026-04-27

54

Participants Needed

6

Research Sites

39 weeks

Total Duration

On this page

Sponsors

V

Vanderbilt-Ingram Cancer Center

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating whether genetic testing of tumor tissue can help select the best treatment for patients with advanced or metastatic clear cell renal cell carcinoma (kidney cancer). This phase II trial focuses on two FDA-approved treatment combinations: one with two immunotherapy drugs given by intravenous infusion (nivolumab plus ipilimumab) and another combining one immunotherapy infusion (nivolumab) with an oral targeted therapy pill (cabozantinib). The study aims to see if matching treatment to the tumor's genetic makeup can improve treatment response. Participants are assigned to one of two treatment arms based on the tumor's RNA sequencing results. In Arm I, patients receive ipilimumab and nivolumab infusions every 21 days for four cycles, followed by nivolumab maintenance infusions every 4 weeks if there is no disease progression or unacceptable side effects. In Arm II, patients receive nivolumab infusion on day 1 and take cabozantinib pills daily, with cycles repeating every 4 weeks under similar conditions. After treatment, patients are followed up within 30 days of the last dose. During the study, participants will have tumor tissue tested for genetic clusters to guide treatment choice. Researchers will monitor treatment response using overall response rates and progression-free survival, assess side effects including immune-related events, and analyze tissue and blood samples to understand treatment effects. The trial may last up to four years, with regular treatment cycles and follow-up visits to evaluate patient outcomes and safety.

CONDITIONS

Brief Title

Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histological confirmation of renal cell carcinoma with a clear cell component
  • Advanced or metastatic renal cell carcinoma not suitable for curative surgery or radiation
  • Ability to understand and sign the informed consent form
  • Male or female 18 years of age or older
  • Karnofsky performance status of 70% or higher
  • No prior systemic therapy for renal cell carcinoma in any setting
  • At least one measurable lesion according to RECIST 1.1 criteria
  • Availability of tumor tissue suitable for RNA sequencing (excluding bone metastasis tissue without soft tissue)
  • Assigned to RNAseq cluster 1, 2, 4, or 5 (clusters 3, 6, 7 are excluded)
  • Adequate kidney function with creatinine clearance 30 mL/min or higher
  • Adequate liver function with total bilirubin ≤1.5 times upper limit of normal (except Gilbert's syndrome), ALT and AST ≤3 times upper limit of normal
  • Women of childbearing potential must have a negative pregnancy test before treatment
Not Eligible

You will not qualify if you...

  • Major surgery requiring general anesthesia within 14 days before treatment
  • Uncontrolled hypertension with blood pressure over 160/90 mmHg despite medication
  • Active infection requiring intravenous treatment
  • Preexisting gastrointestinal or non-gastrointestinal fistula
  • Proteinuria greater than 2 g in 24 hours
  • Non-healing wounds (for patients assigned to nivolumab plus cabozantinib)
  • Clinically significant active bleeding including coughing up blood
  • Inability to swallow oral medication or uncontrolled gastrointestinal disorders affecting drug absorption (for nivolumab plus cabozantinib patients)
  • Significant cardiovascular disease including class III or IV heart failure, unstable angina within 3 months, or recent heart attack within 3 months
  • Central nervous system metastases unless local therapy completed
  • Use of systemic corticosteroids over 10 mg prednisone (or equivalent) daily or other immunosuppressive medications within 14 days before treatment
  • Except for minimal systemic corticosteroids use such as topical or low-dose physiologic replacement

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Up to 4 years

Participants receive assigned front-line therapy based on their RNA sequence-defined biologic cluster. Arm I includes 4 cycles of ipilimumab and nivolumab IV every 21 days followed by maintenance nivolumab IV every 4 weeks. Arm II includes nivolumab IV on day 1 and daily oral cabozantinib in 4-week cycles until disease progression or unacceptable toxicity.

Cycles repeat every 3 or 4 weeks depending on treatment phase

Follow-up

Duration - Within 30 days after treatment ends

Participants are followed up within 30 days after the last dose to assess outcomes and safety.

1 visit (in-person)

Trial Site Locations

Total: 6 locations

1

City of Hope National Medical Center

Duarte, California, United States, 91010

Actively Recruiting

2

Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

Actively Recruiting

3

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States, 44106

Actively Recruiting

4

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Actively Recruiting

5

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States, 37232

Actively Recruiting

6

University of Texas, Southwestern Medical Center

Dallas, Texas, United States, 75390

Actively Recruiting

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Research Team

V

Vanderbilt-Ingram Service for Timely Access

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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