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Combination treatment of Nivolumab and Ipilimumab for rare subtype sarcoma

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)

Phase 3 Interventional Centre Leon Berard · NCT04741438

This study is testing if a combination of two cancer drugs, Nivolumab and Ipilimumab, can help people with rare types of advanced sarcoma live longer without their disease getting worse compared to another drug called Pazopanib.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment96 (estimated)
Ages18 Years and up
SexAll
SponsorCentre Leon Berard Academic / other
Drugs / interventionsnivolumab, ipilimumab, chemotherapy, immunotherapy, radiation, methotrexate, cyclophosphamide, prednisone
Locations13 sites (Strasbourg, Bas-Rhin and 12 other locations)
Trial IDNCT04741438 on ClinicalTrials.gov

What this trial studies

This phase 3 clinical trial is a randomized open-label study comparing the efficacy of the combination of Nivolumab and Ipilimumab against Pazopanib in patients with metastatic or unresectable advanced sarcoma of rare subtypes. Eligible patients will be randomly assigned to receive either the combination treatment for up to 24 months or Pazopanib alone. The study aims to determine if the combination therapy can improve progression-free survival compared to the control. Patients will be monitored for disease status and survival after treatment completion.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed metastatic or unresectable advanced sarcoma of specific rare subtypes.

Not a fit: Patients with sarcomas that are not of the specified rare subtypes or those who have not been previously treated with an anthracycline-based regimen may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with rare subtype sarcomas that are resistant to standard therapies.

How similar studies have performed: Other studies have shown promising results with immunotherapy combinations in various cancers, suggesting potential success for this novel approach in rare sarcoma subtypes.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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)
* SMARCA-4 deficient sarcoma
* Malign Peripheral Nerve Sheath Tumours (MPNST)
* Chordoma;

I3. Metastatic disease or unresectable locally advanced malignancy that is resistant or refractory to standard therapy or for which standard therapy does not exist or is not considered appropriate by the Investigator;

I4. Measurable disease as per the RECIST version 1.1;

I5. Previously treated with anthracycline-based regimen except for whom standard therapy does not exist or is not considered appropriate by the Investigator: inclusion in first line is allowed (randomisation will be stratified according to the number of previous treatment lines);

I6. Performance Status (ECOG) of 0 or 1;

I7. Patients must have an adequate organ and bone marrow function at baseline;

* Absolute neutrophil count (ANC) ≥ 1.0 x 10 G/L
* Platelets ≥ 100 x 10 G/L
* Haemoglobin ≥ 9 g/dL (without transfusion within 7 days)
* Serum creatinine OR Calculated creatinine clearance as per MDRD or CKD-EPI formula ≤ 1.5 upper limit of normal (ULN) OR ≥ 40 mL/min /1.73m2
* Serum total bilirubin ≤ 1.5 ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤ 3ULN is acceptable).
* AST and ALT ≤ 3 ULN
* International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 ULN

I8. Women of childbearing potential must have a negative serum pregnancy test within 7 days before C1D1.

I9. Women of childbearing potential must agree to use 1 highly effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drugs.

I10. Ability to understand and willingness for follow-up visits;

I11. Covered by a medical insurance;

I12. Signed and dated informed consent document indicating that the patient has been informed of all aspects of the trial prior to enrolment.

Exclusion Criteria:

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
* Live vaccines. Note: Influenza vaccination should be given during influenza season. Patients must not receive live attenuated influenza vaccine (e.g., FluMist®) : 4 weeks
* Systemic immunostimulatory agents, including but not limited to IFN-α, IFN-γ, or IL-2 : 4 weeks
* Immunosuppressive medication (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) with the exceptions of intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone (or 0.1mg/kg for pediatric patients), or an equivalent corticosteroid :2 weeks
* P-gp inhibitors : None
* Strong or moderate inhibitors of CYP3A4 : None
* Strong CYP3A4 inducers : None
* Oral or IV antibiotics :2 weeks

Note: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection, pneumocystis or chronic obstructive pulmonary disease exacerbation) are eligible.

E6. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:

* patients with a history of autoimmune-related hypothyroidism who are on stable thyroid replacement hormone therapy,
* patients with controlled Type 1 diabetes mellitus,
* patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are eligible provided that they meet the following conditions:

  * Rash must cover less than 10% of body surface area (BSA).
  * Disease is well controlled at baseline and only requiring low potency topical steroids.
  * No acute exacerbations of underlying condition within the previous 12 months requiring psoralen plus ultraviolet A radiation (PUVA), methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids;

E7. Patients with HIV, active B or C hepatitis infection, or any other active infection.

E8. Patients with active tuberculosis;

E9. Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past;

E10. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan;

E11. Patients with a high-risk of hemorrhage or history of coagulopathy;

E12. Any contraindication to nivolumab, to ipilimumab or to pazopanib according to the Summary of Product Characteristics of each drug;

E13. History of other malignancy other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of disease for at least 3 years;

E14. Patient under tutorship or curatorship or deprived of liberty;

E15. Pregnant or breast-feeding woman

Where this trial is running

Strasbourg, Bas-Rhin and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions SarcomaSarcoma of rare subtypeMetastatic sarcomaUnresectable advanced sarcomaNivolumabIpilimumabRandomizationPazopanib
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.