A BIOmarker Driven Trial With Nivolumab and Ipilimumab or VEGFR tKi in Naïve Metastatic Kidney Cancer

Conditions

• Clear Cell Metastatic Renal Cell Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Nivolumab — DRUG
  For Arms 1A and 4A: Nivolumab alone administered IV over 60 minutes at 240 mg every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. For Arms 1B, 2B, 3B and 4B: Nivolumab administered IV over 60 minutes at 3 mg/kg combined with ipilimumab administered IV over 30 minutes at 1 mg/kg every 3 weeks for 4 doses followed by nivolumab administered IV over 60 minutes at 240 mg every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Ipilimumab — DRUG
  For Arms 1B, 2B, 3B and 4B: Ipilimumab administered IV over 30 minutes at 1 mg/kg every 3 weeks combined with Nivolumab administered IV over 60 minutes at 3 mg/kg for 4 doses until disease progression, unacceptable toxicity or other reasons specified in the protocol.
• Pazopanib — DRUG
  For Arms 2C and 3C (TKI pazopanib or sunitinib): Pazopanib 800 mg orally QD until disease progression, unacceptable toxicity or other reasons specified in the protocol
• Sunitinib — DRUG
  For Arms 2C and 3C (TKI pazopanib or sunitinib): Sunitinib 50 mg orally QD until disease progression, unacceptable toxicity or other reasons specified in the protocol

Study Details

Disease and Stage: naïve metastatic kidney cancer. A multicenter, randomized, a Phase 2 BIOmarker driven trial with Nivolumab and Ipilimumab or VEGFR tKi in naïve metastatic Kidney cancer

Key Dates

Start date

May 31, 2017

Status verified

Apr 2021

Primary completion

Feb 15, 2021

Completion

Feb 15, 2021

Study Design

Enrollment

200 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: ccRCC molecular subgroup 1: 1A
  ccRCC molecular subgroup 1 -\> randomisation: subjects with ccRCC1 treated with nivolumab 240mg IV every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Experimental: ccRCC molecular subgroup 1: 1B
  ccRCC molecular subgroup 1 -\> randomisation: subjects with ccRCC1 treated with nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then nivolumab 240mg IV every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Experimental: ccRCC molecular subgroup 4: 4A
  ccRCC molecular subgroup 4 -\> randomisation: subjects with ccRCC1 treated with nivolumab 240mg IV every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Experimental: ccRCC molecular subgroup 4: 4B
  ccRCC molecular subgroup 4 -\> randomisation: subjects with ccRCC1 treated with nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then nivolumab 240mg IV every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Experimental: ccRCC molecular subgroup 2: 2C
  ccRCC molecular subgroup 2 -\> randomisation: TKI (sunitinib 50mg daily or Pazopanib 800mg daily) according to investigator's choice until disease progression, unacceptable toxicity or other reasons specified in the protocol.
• Experimental: ccRCC molecular subgroup 2: 2B
  ccRCC molecular subgroup 2 -\> randomisation: subjects with ccRCC1 treated with nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then nivolumab 240mg IV every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Experimental: ccRCC molecular subgroup 3: 3B
  ccRCC molecular subgroup 3 -\> randomisation: subjects with ccRCC1 treated with nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then nivolumab 240mg IV every 2 weeks until disease progression, unacceptable toxicity or other reasons specified in the protocol. Starting from the Cycle 7 possibility to switch from nivolumab 240 mg every 2 weeks to 480 mg every 4 weeks according to the Investigator's preference.
• Experimental: ccRCC molecular subgroup 3: 3C
  ccRCC molecular subgroup 3 -\> randomisation: TKI (sunitinib 50mg daily or Pazopanib 800mg daily) according to investigator's choice until disease progression, unacceptable toxicity or other reasons specified in the protocol.

Primary Outcome Measure

ORR evaluation according to molecular groups (ccRCC1 to 4) and assigned treatment [ Time Frame: 54 months ]