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MelanomaPhase 1/2NCT03354962

Induction of Immune-mediated aBscOpal Effect thrOugh STEreotactic Radiation Therapy in Metastatic Melanoma Patients Treated by PD-1 + CTLA-4 Inhibitors (BOOSTER MELANOMA)

A Phase 1/2 study testing Nivolumab + Ipilimumab and Combined treatment schema in people with Melanoma, run by Institut Claudius Regaud at 6 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is a phase I/II, multicenter, open-label study starting with a phase I part followed by a Phase II part. The phase I part of the study aims at evaluating the safety and efficacy (in terms of abscopal effect at week 6) of the treatment combination schema of Stereotactic Body Radiation Therapy (SBRT) and PD-1… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Nivolumab + Ipilimumab and Combined treatment schema
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
6 sitesFrance
Study dates
15 Oct 2018to 27 Oct 2020
Phase
Phase 1/2
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

  • Patients with histologically-proven metastatic and/or unresectable melanoma (stage IIIc-IV, M1a-c as per AJCC 8th Edition), including mucosal melanoma, without evidence of active intra-cranial disease.
  • Patients with tumor PD-L1 expression <1%.
  • Patients are included regardless of BRAFV600 mutation status. BRAFV600 mutation status must be documented.
  • Patients with a metastatic lesion located on liver, lung, or bone and eligible for a SBRT.
  • Patients should present at least two lesions: one lesion to be irradiated and one distant lesion that will serve as control. Lesion to be irradiated will be selected on the basis of symptomatology, safety and/or location. Preferentially, both lesions should be measurable per RECIST 1.1. If only the control lesion is measurable but not the irradiated lesion, eligibility will be discussed with the sponsor.
  • Age ≥18 years at the time of study entry.
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  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  • Life expectancy of at least 3 months.
  • Patients able to participate and willing to give informed consent prior to performance of any study-related procedures and to comply with the study protocol.
  • Screening laboratory values must meet the following criteria and should be obtained prior to commencement of treatment:
  • White blood count (WBC) ≥ 2000/μL
  • Neutrophils ≥ 1500/μL
  • Platelets ≥ 100 x103/μL
  • Hemoglobin > 9.0 g/dL
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula)
  • AST/ALT ≤ 3 x ULN (except subjects with hepatic metastasis, who can have AST/ALT ≤ 5 x ULN)
  • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Adequate cardiac and respiratory functions defined as New York Heart Association (NYHA) class 1 and SaO2 > 90%.
  • Patient must be naïve to systemic treatment for locally advanced and/or metastatic disease (i.e., no prior systemic anticancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant therapies (including Interferon α and Ipilimumab) is permitted if it was completed at least 12 weeks before start of treatment and all related AEs have either returned to baseline or stabilized.
  • Prior radiotherapy or radiosurgery must have been completed at least 4 weeks prior to the first dose of the study treatment.
  • Women of childbearing potential (WOCBP) must use two appropriate methods of contraception to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab/Ipilimumab to undergo five half-lives) after the last dose of investigational drug.
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
  • Men who are sexually active with WOCBP must use two contraceptive methods including at least one method with a failure rate of less than 1% per year for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception
  • Absence of any psychological, familial, sociological or geographical condition that potentially hampers compliance with the study protocol and follow-up after treatment discontinuation schedule.
  • Patient affiliated to a Social Health Insurance in France.

Who cannot join

  • Patient pregnant, or breast-feeding.
  • Uveal melanoma.
  • Active and/or symptomatic intra cranial metastasis (including melanomatous meningitis).
  • Previous treatment with B-RAF or MEK inhibitors within 12 weeks prior start of treatment.
  • Hypersensitivity to the drugs of the study.
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
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  • Clinically significant cardiac dysfunction including congenital, familial, and genetic cardiac disorders, current instable angina, current symptomatic congestive heart failure of NYHA class 2 and higher, current uncontrolled hypertension ≥ grade 3; Left Ventricular Ejection Fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower.
  • Patient with active malignancy other than melanoma or a history of previous within the past 3 years; except for patients with resected Basal cell carcinoma or resected Spindle cell carcinoma, resected carcinoma in situ of the cervix and resected carcinoma in situ of the breast.
  • Active, known or suspected autoimmune disease including but not restricted to multiple sclerosis, optical nevritis and demyelinating neuropathy. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (ribonucleic acid or HCV antibody) indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Vaccination with any live attenuated conventional vaccine within the 3 months preceding the start of study treatment.
  • Any current severe or uncontrolled disease, including, but not limited to ongoing or active infection.
  • Patient included in another study with an experimental molecule and/or procedure.
  • Unwillingness or inability to provide written informed consent.
  • Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the compliance of treatment and the study protocol.
  • Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

France6 sites

  • Chu Bordeaux

    Bordeaux

  • Centre Oscar Lambret

    Lille

  • ICM

    Montpellier

  • CHU NICE

    Nice

  • Centre Eugene Marquis

    Rennes

  • Institut Universitaire du Cancer de Toulouse - Oncopole

    Toulouse, 31059

Other trials in France

About this study

This study is a phase I/II, multicenter, open-label study starting with a phase I part followed by a Phase II part.

The phase I part of the study aims at evaluating the safety and efficacy (in terms of abscopal effect at week 6) of the treatment combination schema of Stereotactic Body Radiation Therapy (SBRT) and PD-1 plus CTLA-4 inhibitors in patients with metastatic melanoma. Patients will be assigned in one of 3 cohorts depending the metastatic site. 18 patients will be enrolled in each cohort.

Read more

Once the recommended optimal radiotherapy dose has been declared for the 3 cohorts, patients will be enrolled in the phase II part of the study in order to evaluate the activity (progression-free survival at 6 months) of SBRT given in combination with immune checkpoints inhibitors in patients with metastatic melanoma.

66 patients will be included in the phase II.

Conditions
Melanoma
Being tested
Nivolumab + Ipilimumab, Combined treatment schema
Keywords
Melanoma, Immune checkpoint, Nivolumab, Ipilimumab, Abscopal effect, Stereotactic radiotherapy, PD-1, CTLA-4
Medical subject headings
Melanoma, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

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

  • Nivolumab + IpilimumabCombination product

    Nivolumab + Ipilimumab alone (standard dosage regimen)

  • Combined treatment schemaCombination product

    SBRT (recommended optimal dose) with Nivolumab + Ipilimumab (standard dosage regimen)

Study groups in NCT03354962
Study groupRoleWhat they receive
ARM AActive comparatorNot described
Receives: Combination Product: Nivolumab + Ipilimumab
ARM BExperimentalNot described
Receives: Combination Product: Combined treatment schema

What is being measured

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

  1. Phase I: Dose Limiting Toxicities (DLT) incidence.

    Measured: 3 weeks per patient

  2. Phase I: Abscopal effect.

    Abscopal effect is defined as a tumor shrinkage ≥ 20% compared to baseline in the control lesion (non-irradiated and distant lesion) at the end of the 6-week period of treatment without evidence of clinical progression.

    Measured: 6 weeks per patient

  3. Phase II: The primary endpoint is the rate of patients alive without progression at 6 months.

    Measured: 6 months per patient

Secondary outcomes (4)

  1. Phase I: Safety will be evaluated using NCI CTCAE V4.03 criteria.

    Measured: 15 months per patient

  2. Phase II: Progression Free Survival (PFS) is defined as the time from inclusion until progression or death.

    Measured: 24 months per patient

  3. Phase II: Safety will be evaluated using NCI CTCAE V4.03.

    Measured: 15 months per patient

  4. Phase II: Pattern of response rate will be followed in irradiated and non-irradiated lesions separately by CT-scan evaluation using RECIST V1.1.

    Measured: 24 months per patient

Timeline

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

  1. First posted28 Nov 2017
  2. Study start15 Oct 2018
  3. Primary completion20 Feb 2020
  4. Study completion27 Oct 2020

Why it stopped: Slow recruitment rate

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03354962
Sponsor's protocol ID
17 CUTA 11
Status last verified
Dec 2020
First submitted
16 Nov 2017
Last updated
4 Dec 2020
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 1/2 study testing Nivolumab + Ipilimumab and Combined treatment schema in people with Melanoma, run by Institut Claudius Regaud at 6 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 25 inclusion and 17 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: stopped early, as of the sponsor's last update on 4 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was stopped early (reason given: Slow recruitment rate). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Dose Limiting Toxicities (DLT) incidence. (time frame: 3 weeks per patient). The study lists 3 primary outcomes in all. 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 NCT03354962.

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 4 Dec 2020.

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