Efficacy of the Combination of Nivolumab and Ipilimumab as a Treatment in Patients With Sarcoma of Rare Subtype

NCT04741438 | Unknown Phase 3 DMC

• 1 other identifier: ET 20-128_RAR-IMMUNE
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 13

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.

Conditions

Sarcoma

Keywords

Sarcoma of rare subtype; Metastatic sarcoma; Unresectable advanced sarcoma; Nivolumab; Ipilimumab; Randomization; Pazopanib; Progression free-survival; Best Overall Response; Objective response rate; Duration of response; Time to treatment failure; Overall survival; Quality of Life; Tolerance profile

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  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.

  up to 36 months

Secondary Outcomes (7)

• Best Overall Response (BOR)

  up to 36 months

• Objective Response Rate (ORR)

  up to 36 months

• Duration of Response (DOR)

  up to 36 months

• Time to Treatment Failure (TTF)

  up to 36 months

• Overall Survival (OS)

  up to 36 months

Study Arms (2)

Arm A

EXPERIMENTAL

Arm A (Experimental arm). * Nivolumab 3 mg/kg * Ipilimumab 1 mg/kg

Drug: Nivolumab and IPILIMUMAB

Arm B

ACTIVE COMPARATOR

Arm B (Control arm). Pazopanib 800 mg/day

Drug: Pazopanib Oral Tablet [Votrient]

Interventions

Nivolumab and IPILIMUMAB DRUG

The combination of Nivolumab+Ipilimumab will be given to patients as follows: * Nivolumab: 3 mg/kg IV over 30 minutes every 2 weeks for 4 cycles. * Ipilimumab 1 mg/kg IV over 60 minutes every 6 weeks for 4 cycles. After completion of 4 courses with ipilimumab, patients continue receiving nivolumab IV at the dose of 480 mg Q4W in the absence of disease progression or unacceptable toxicity for a maximum of 18 months. Nota Bene: A cycle is defined as a 6-weeks period. The planned treatment period is 24 months Nivolumab and Ipilimumab must be injected the same day every 6 weeks (Q6W). In case of toxicity, dose will be delayed, but will not be reduced.

Arm A

Pazopanib Oral Tablet [Votrient] DRUG

Treatment by pazopanib 800 mg/day per os, continuously during a maximum 24 months. In case of toxicity, dose will be delayed and reduced.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Age ≥ 18 years at the day of consenting to the study;
• I2. 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)
• Solitary Fibrous Tumour (SFT)
• Epithelioid HemangioEndothelioma (EHE)
• Inflammatory Myofibroblastic Tumour (IMT)
• Epithelioid sarcoma (ES)
• FibroSarcoma (FS)

You may not qualify if:

• E1. Concurrent use of any other approved or investigational antineoplastic agent;
• E2. Prior or concurrent treatment with any antibody targeting PD1, PDL1, PDL2 or CTLA4;
• E3. Prior treatment with pazopanib;
• E4. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Note:
• 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;
• E5. 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
• Radiotherapy Note: palliative radiotherapy on non-target lesions is allowed. : 3 weeks
• Surgery
• Major surgical procedure, open biopsy, or significant traumatic injury : 4 weeks
• Abdominal surgery, abdominal interventions or significant abdominal traumatic injury : 60 days

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (13)

Institut de cancérologie Strasbourg Europe

Strasbourg, Bas-Rhin, 67033, France

RECRUITING

Centre Léon Bérard

Lyon, Rhône, 69373, France

RECRUITING

Hôpital Jean Minjoz

Besançon, 25030, France

RECRUITING

Institut Bergonié

Bordeaux, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

Centre Oscar Lambret

Lille, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Hôpital Cochin

Paris, France

NOT YET RECRUITING

CHU de Poitiers

Poitiers, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

Institut Claudius Regaud - IUCT Oncopole

Toulouse, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Nivolumab; Ipilimumab; pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Séverine METZGER

CONTACT

+33(0)478782786; severine.metzger@lyon.unicancer.fr

Mehdi BRAHMI

CONTACT

Mehdi.BRAHMI@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 5, 2021
• Study Start: March 30, 2021
• Primary Completion: February 1, 2025
• Study Completion: August 1, 2025
• Last Updated: August 30, 2023

Record last verified: 2023-08

Locations

FR (13)