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SarcomaPhase 3RAR-ImmuneNCT04741438

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

A Phase 3 study testing Nivolumab and IPILIMUMAB and Pazopanib Oral Tablet [Votrient] in people with Sarcoma, run by Centre Leon Berard at 13 sites in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoma
What is being tested?
Nivolumab and IPILIMUMAB and Pazopanib Oral Tablet [Votrient]
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
13 sitesFrance
Study dates
30 Mar 2021to Aug 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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.
Show all 39Show fewer
  • 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

Trial locations and contacts

13 sites in 1 country.

Séverine METZGER contact

+33(0)478782786

severine.metzger@lyon.unicancer.fr

Mehdi BRAHMI contact

Mehdi.BRAHMI@lyon.unicancer.fr

13 sites in 1 country

France13 sites, 13 recruiting

  • Hôpital Jean Minjoz

    Besançon, 25030

    Loïc CHAIGNEAU, lchaigneau@chu-besancon.fr

    Recruiting

  • Institut Bergonié

    Bordeaux

    Antoine Italiano, MD, 05.56.33.32.44 ext. +33, a.italiano@bordeaux.unicancer.fr

    Recruiting

  • Centre Georges François Leclerc

    Dijon

    Alice Hervieu, MD, ahervieu@cgfl.fr

    Recruiting

  • Centre Oscar Lambret

    Lille

    Nicolas Penel, MD, n-penel@o-lambret.fr

    Recruiting

  • Centre Léon Bérard

    Lyon, Rhône, 69373

    Mehdi BRAHMI, mehdi.brahmi@lyon.unicancer.fr

    Mehdi BRAHMI, Dr

    Recruiting

  • Institut Paoli Calmettes

    Marseille

    François Bertucci, MD, bertuccif@ipc.unicancer.fr

    Not yet recruiting

  • Centre Antoine Lacassagne

    Nice

    Agnès Ducoulombier, MD, agnes.ducoulombier@nice.unicancer.fr

    Recruiting

  • Hôpital Cochin

    Paris

    Camille Tlemsani, MD, camille.tlemsani@aphp.fr

    Not yet recruiting

  • CHU de Poitiers

    Poitiers

    Nicolas Isambert, MD, nicolas.isambert@chu-poitiers.fr

    Not yet recruiting

  • Centre Eugène Marquis

    Rennes

    Christophe Perrin, MD, c.perrin@rennes.unicancer.fr

    Recruiting

  • Institut de cancérologie Strasbourg Europe

    Strasbourg, Bas-Rhin, 67033

    Justine GANTZER, j.gantzer@icans.eu

    Recruiting

  • Institut Claudius Regaud - IUCT Oncopole

    Toulouse

    Thibaud Valentin, MD, valentin.thibaud@iuct-oncopole.fr

    Recruiting

  • Institut Gustave Roussy

    Villejuif

    Benjamin Verret, MD, benjamin.verret@gustaveroussy.fr

    Recruiting

Other trials in France

About this study

Official title: 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)

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.

Read the 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.

Conditions
Sarcoma
Being tested
Nivolumab and IPILIMUMAB, Pazopanib Oral Tablet [Votrient]
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
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nivolumab and IPILIMUMABDrug

    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.

  • 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.

Study groups in NCT04741438
Study groupRoleWhat they receive
Arm AExperimentalArm A (Experimental arm). * Nivolumab 3 mg/kg * Ipilimumab 1 mg/kg
Receives: Drug: Nivolumab and IPILIMUMAB
Arm BActive comparatorArm B (Control arm). Pazopanib 800 mg/day
Receives: Drug: Pazopanib Oral Tablet [Votrient]

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 36 months

Secondary outcomes (7)

  1. Best Overall Response (BOR)

    The Best Overall Response will be defined as the best among all overall responses during the trial.

    Measured: up to 36 months

  2. Objective Response Rate (ORR)

    The Objective Response Rate will be defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) during the trial.

    Measured: up to 36 months

  3. Duration of Response (DOR)

    in the patients whose BOR is either CR or PR, the DOR will be defined as the time from the date of first documented tumour response to the date of first documented disease progression or death due to underlying cancer. Patients with no event at the time of the analysis will be censored.

    Measured: up to 36 months

  4. Time to Treatment Failure (TTF)

    The Time to Treatment Failure will be defined as the time from the date of randomisation to the date of permanent study treatments discontinuation (any cause, including disease progression, treatment toxicity, adverse event, start of any new anticancer therapy, withdrawal of consent and death). Patients without treatment failure at the time of the analysis will be censored at the date of last tumour

    Measured: up to 36 months

  5. Overall Survival (OS)

    The Overall Survival will be defined as the time from the date of randomisation to the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

    Measured: up to 36 months

  6. Quality of Life (QoL)

    The Quality of Life will be assessed using the EORTC QLQ-C30 questionnaire.

    Measured: up to 36 months

  7. Tolerance profile

    The Tolerance profile will be described through the incidence and severity of drug-related AEs according to the Common Terminology Criteria for Adverse Events (CTCAE) (v5.0)

    Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2021
  2. Study start30 Mar 2021
  3. Primary completionFeb 2025 (estimated)
  4. Study completionAug 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04741438
Sponsor's protocol ID
ET 20-128_RAR-IMMUNE
Acronym
RAR-Immune
Status last verified
Aug 2023
First submitted
2 Feb 2021
Last updated
30 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab and IPILIMUMAB and Pazopanib Oral Tablet [Votrient] in people with Sarcoma, run by Centre Leon Berard at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Séverine METZGER (+33(0)478782786, severine.metzger@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04741438.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2023.

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