Nivolumab Plus Radiotherapy in Advanced Melanoma

NCT02799901 | Completed Phase 2

• 1 other identifier: 16-PP-02
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 14

Brief Summary

Combining nivolumab with conventional multisite high dose radiotherapy seems to be an interesting approach that could increase the antitumoral effect of nivolumab by increasing the diversity and quantity of tumoral antigen presentation thanks to radiotherapy. Multifractionated high dose radiotherapy (HR) targeting various tumor sites could also increase occurrence of tumor mutations and the diversity of the T-cell receptor repertoire of intratumoral T cells. The purpose of this study is to combine nivolumab with 3 fractions of HR of one metastasis for each tumor site (defined as skin/muscle, thoracic, abdomen, bone, other). The investigators hypothesize that combining nivolumab with multisite, multifractionated HR increases the overall survival rate at 1 year compared to published data with nivolumab alone.

Conditions

Melanoma

Keywords

advanced melanoma; high dose radiotherapy; Nivolumab

Outcome Measures

Primary Outcomes (1)

• overall survival

  to increase the overall survival rate at 1 year with the combination of nivolumab and radiotherapy compared to nivolumab alone for patients with advanced melanoma

  1 year

Secondary Outcomes (12)

• the rate of progression-free survival

  at 6 months

• the rate of progression-free survival

  at 1 year

• the rate of progression-free survival

  at 2 years

• Global progression free survival (PFS) rate

  at 6 months

• Global progression free survival (PFS) rate

  at 1 year

Study Arms (1)

Patient

EXPERIMENTAL

patient with Advanced melanoma

Biological: Nivolumab; Radiation: hypofractionned radiotherapy

Interventions

Nivolumab BIOLOGICAL

Injection of nivolumab

Patient

hypofractionned radiotherapy RADIATION

radiation

Patient

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent
• Men and women, ≥ 18 years of age
• Histologically confirmed Stage III (unresectable) or Stage IV melanoma. Unknown primary melanoma will be accepted.
• Measurable disease by CT per RECIST 1.1 criteria
• Indication of radiotherapy
• Patient MUST be untreated for his/her Stage III (unresectable) or Stage IV melanoma
• Prior treatment with INTERFERON in the adjuvant setting is authorized.
• BRAF status must be determinate but patient will be eligible regardless the status (BRAF wildtype and BRAF V600 mutation positive patients could be included)
• Patient must consent to allow the acquisition of existing formalin-fixed paraffin-embedded (FFPE) material (" archival ") (block or a minimum of 10 unstained slides) if available, for performance of correlatives studies
• Subjects must consent to allow the acquisition of blood samples: one during the week before the first nivolumab injection; the second 15 days +- 2 days after the first injection of nivolumab; the third between 15 and 30 days after the first radiotherapy session and the fourth at relapse, for performance of correlative studies,
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
• Within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified:
• Subjects affiliated to an appropriate social security system NB: Patients will be included regardless of the level of LDH.

You may not qualify if:

• Patient with brain(s) metastase(s), symptomatic(s) or not,
• Ocular or mucosal melanoma (unknown primary melanoma will be accepted),
• The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk such as but not limited to: Cardiac insufficiency (III or IV as per NYHA classification), Renal insufficiency, ongoing infection,
• Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, gastric or colon cancers, cervical cancers/dysplasia or breast carcinoma in situ) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period,
• Uncontrolled infectious diseases - requires negative tests for clinically suspected HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). If positive results are not indicative of true active or chronic infection, the subject may enter the study after discussion and agreement between the Investigator and the Medical Monitor,
• Active Autoimmune disease: subjects with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease are excluded from this study as are subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); subjects with 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 are permitted to enroll,
• Subjects with motor neuropathy considered of autoimmune origin (e.g., Guillain Barré Syndrome) are excluded from this study,
• Previous treatment with, chemotherapy, a CTLA-4 or PD-1/PD-L1 antagonist agent, including treatment in adjuvant setting for immunotherapy,
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures,
• Lack of availability for clinical follow-up assessments,
• Pregnant or lactating women (a blood pregnancy test will be conducted) and effective contraception will be used throughout the treatment for women of childbearing age,
• Participation in another clinical trial protocol within 30 days prior to enrolment,
• Persons protected by a legal regime (guardianship, trusteeship),
• Vulnerable patients, patients kept in detention

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (14)

CHU d'Amiens

Amiens, France

Location

CH d'Annecy

Annecy, France

Location

CHRU de Besançon

Besançon, France

Location

Hôpital Ambroise Paré

Boulogne-Billancourt, France

Location

Hôpital Avicenne

Boulogne-Billancourt, France

Location

CHU Hôpital Clemenceau

Caen, France

Location

CHU de Clermont Ferrand

Clermont-Ferrand, France

Location

CHRU de Lille

Lille, France

Location

Hôpital Dupuytren

Limoges, France

Location

Hospices civiles de Lyon

Lyon, France

Location

CHU La Timone

Marseille, France

Location

CHU de NIce

Nice, 06200, France

Location

Hôpital St Louis

Paris, France

Location

CHU de Rouen

Rouen, France

Location

Related Publications (1)

• Gerard A, Doyen J, Cremoni M, Bailly L, Zorzi K, Ruetsch-Chelli C, Brglez V, Picard-Gauci A, Troin L, Esnault VLM, Passeron T, Montaudie H, Seitz-Polski B. Baseline and early functional immune response is associated with subsequent clinical outcomes of PD-1 inhibition therapy in metastatic melanoma patients. J Immunother Cancer. 2021 Jun;9(6):e002512. doi: 10.1136/jitc-2021-002512.

  PMID: 34088741 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

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 Officials

• Henri MONTAUDIE, PH

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2016
• First Posted: June 15, 2016
• Study Start: March 3, 2017
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: November 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14)