Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer

Sponsor
The Netherlands Cancer Institute
Study ID
NCT05148546
Phase
PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Neoadjuvant nivolumab — DRUG
    Patients will receive 2 cycles of nivolumab 360mg (arm A and C) or 3mg/kg (arm B) every 3 weeks followed by a nephrectomy.
  • Neoadjuvant ipilimumab — DRUG
    Patients will receive 2 cycles of ipilimumab 1mg/kg every 3 weeks followed by a nephrectomy.
  • Neoadjuvant relatlimab — DRUG
    Patients will receive 2 cycles of relatlimab 360mg every 3 weeks followed by a nephrectomy.

Study Details

The NESCIO-trial is a multicenter, randomized, open-label, three-arm phase II trial investigating different combinations of neoadjuvant immunotherapy in patients with primary, resectable, intermediate to high-risk, clear-cell renal cell carcinoma. In this trial patients will be randomized 1:1:1 to receive either 2 cycles of nivolumab 360mg every 3 weeks (arm A), 2 cycles of ipilimumab 1 mg/kg + nivolumab 3 mg/kg every 3 weeks (arm B) or 2 cycles of relatlimab 360mg + nivolumab 360mg every 3 weeks (arm C), prior to surgery at week 7. After 42 patients (14 per arm) have been recruited, an interim analysis will be performed to evaluate the observed efficacy and toxicity within each arm and either allow for early discontinuation of the treatment or continuing recruitment for the second stage. As the primary endpoint, the pathological response (decrease in tumor) will be evaluated. If at most one pathologic response in the primary tumor is observed, the treatment arm will be closed for insufficient activity on the primary tumor. If at least 2 pathologic responses are observed, 9 additional patients will be included to a total of 23 patients per cohort. A maximum of 69 patients will be recruited for this study. Follow up will start at week 12 with a CT-scan according to the national/center's standard. Patients will be evaluated every 3 months by physical examination and lab testing for up to two years, thereafter according to institutional guidelines up to 5 years following surgery.

Key Dates

Start date
Apr 28, 2022
Status verified
Sep 2025
Primary completion
Apr 22, 2025
Completion
Apr 30, 2029

Study Design

Enrollment
69 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: A: Neoadjuvant nivolumab
    Neoadjuvant 2 cycles of nivolumab 360mg every 3 weeks
  • Experimental: B: Neoadjuvant nivolumab + ipilimumab
    Neoadjuvant 2 cycles of nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks
  • Experimental: C: Neoadjuvant nivolumab + relatlimab
    Neoadjuvant 2 cycles of nivolumab 360mg + relatlimab 360mg every 3 weeks

Primary Outcome Measure

Pathologic response rate [ Time Frame: At 6 weeks ]

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