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

NCT03354962 | Terminated Phase 1 DMC

• 1 other identifier: 17 CUTA 11
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief 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 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. 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

Keywords

Melanoma; Immune checkpoint; Nivolumab; Ipilimumab; Abscopal effect; Stereotactic radiotherapy; PD-1; CTLA-4

Outcome Measures

Primary Outcomes (3)

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

  3 weeks per patient

• 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.

  6 weeks per patient

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

  6 months per patient

Secondary Outcomes (4)

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

  15 months per patient

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

  24 months per patient

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

  15 months per patient

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

  24 months per patient

Study Arms (2)

ARM A

ACTIVE COMPARATOR

Combination Product: Nivolumab + Ipilimumab

ARM B

EXPERIMENTAL

Combination Product: Combined treatment schema

Interventions

Nivolumab + Ipilimumab COMBINATION_PRODUCT

Nivolumab + Ipilimumab alone (standard dosage regimen)

ARM A

Combined treatment schema COMBINATION_PRODUCT

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

ARM B

Eligibility Criteria

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

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Institut Claudius Regaud: lead

Study Sites (6)

Chu Bordeaux

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

ICM

Montpellier, France

Location

CHU NICE

Nice, France

Location

Centre Eugene Marquis

Rennes, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Melanoma; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: November 28, 2017
• Study Start: October 15, 2018
• Primary Completion: February 20, 2020
• Study Completion: October 27, 2020
• Last Updated: December 4, 2020

Record last verified: 2020-12

Locations

FR (6)