A Randomised, Comparative, Prospective, Multicentre Study of the Efficacy of Nivolumab + Ipilimumab Versus Pazopanib Alone in Patients With Metastatic or Unresectable Advanced Sarcoma of Rare Subtype (RAR-Immune)
Overview
- Phase
- Phase 3
- Intervention
- Nivolumab and IPILIMUMAB
- Conditions
- Sarcoma
- Sponsor
- Centre Leon Berard
- Enrollment
- 96
- Locations
- 13
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a randomized open label study, with 2 arms treatments conducted in patients with metastatic or unresectable advanced sarcoma of rare subtype; previously treated by anthracycline-based regimen except for whom standard therapy does not exist or is not considered appropriate by the Investigator.
In the experimental arm, patients will receive the combination of Nivolumab + Ipilimumab for a maximum of 24 months, whereas in the control arm, patients will receive Pazopanib alone.
The purpose of the study is to know if the combination of nivolumab + ipilimumab can be more efficient than Pazopanib in terms of Progression-Free Survival.
Detailed Description
This is a randomized open label, comparative, prospective, multicentre phase III study. The patients who meet the eligibility criteria will be randomly assigned (1:1) into one of the following treatments groups: * Experimental arm: Nivolumab + Ipilimumab (24 months maximum) * Control arm: Pazopanib alone (24 months maximum) A randomization procedure will be used to obtain a balanced distribution of stratifications factors: * The number of previous lines of treatment in advanced/metastatic setting: ≤1 line or \>1 line (a treatment line is defined as a treatment initiation whatever the reason) * The lymphocytes count at baseline: \<1 g/L or ≥1 g/L. After their eligibility has been confirmed, patients will be treated with: * The combination of Nivolumab + Ipilimumab for 4 cycles. After completion of 4 cycles with Ipilimumab, patients continue receiving nivolumab IV (480 mg Q4W) in the absence of disease progression or unacceptable toxicity. A cycle is defined as a 6-weeks period. * Or Pazopanib until disease progression or unacceptable toxicity. The planned treatment duration in both arm is maximum 24 months. After the completion of treatment, patients will be followed up within 30 days after the last study treatment administration. The survival and disease status will be updated for all patients at the time of the end of the study. The overall end of the study will be the Last Patient Last Visit (LPLV), defined as the End Of Treatment (EOT) visit of the last active patient.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years at the day of consenting to the study;
- •Only histologically confirmed sarcoma of rare subtype, defined as one of the following subtypes:
- •Angiosarcoma (AS)
- •Alveolar Soft Part Sarcoma (ASPS)
- •Clear Cell Sarcoma (CCSA)
- •Desmoplastic Small Round Cell Tumour (DSRCT)
- •Sclerosing Epithelioid Fibrosarcoma (SEF)
- •Perivascular Epithelioid Cell Tumour (PEComa)
- •Intimal sarcoma (IS)
- •Extraskeletal Myxoid Chondrosarcoma (EMC)
Exclusion Criteria
- •Concurrent use of any other approved or investigational antineoplastic agent;
- •Prior or concurrent treatment with any antibody targeting PD1, PDL1, PDL2 or CTLA4;
- •Prior treatment with pazopanib;
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
- •Asymptomatic patients with treated CNS lesions are eligible.
- •Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan;
- •Patients using, or requirement to use while on the study, or not respecting the minimal wash-out period of medications listed below:
- •Forbidden concomitant medications and minimal wash-out period before Cycle 1 Day1
- •Any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, or immunotherapy : 2 weeks
- •Any investigational agents : 4 weeks
Arms & Interventions
Arm A
Arm A (Experimental arm). * Nivolumab 3 mg/kg * Ipilimumab 1 mg/kg
Intervention: Nivolumab and IPILIMUMAB
Arm B
Arm B (Control arm). Pazopanib 800 mg/day
Intervention: Pazopanib Oral Tablet [Votrient]
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: up to 36 months
The Progression-Free Survival defined as the time from the date of randomisation to the date of first documented progression or death due to any cause. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment.
Secondary Outcomes
- Quality of Life (QoL)(up to 36 months)
- Best Overall Response (BOR)(up to 36 months)
- Objective Response Rate (ORR)(up to 36 months)
- Time to Treatment Failure (TTF)(up to 36 months)
- Duration of Response (DOR)(up to 36 months)
- Overall Survival (OS)(up to 36 months)
- Tolerance profile(up to 36 months)