Ipilimumab Combined With a Stereotactic Radiosurgery in Melanoma Patients With Brain Metastases

NCT02662725 | Completed Phase 2 DMC

• 2 other identifiers: 2011_482012-000852-32
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 18

Brief Summary

This is a non-controlled, open label, Phase II Study of ipilimumab combined with a Stereotactic Radiosurgery. The study included an induction phase of four IV infusions of Ipilimumab at 10 mg/kg every 3 weeks associated with a stereotactic radiosurgery performed 3 days before 2nd ipilimumab administration. A Maintenance phase included Ipilimumab, IV, 10 mg/kg once every 12 weeks, starting at week 24, in the absence of PD, unacceptable toxicity or withdrawal of consent or disease progression. The primary objective is the overall survival. The Secondary objectives include safety, ORR, PFS and peripheral blood absolute lymphocyte count (ALC) as a predictive biomarker.

Conditions

Melanoma; Brain Metastasis

Keywords

melanoma; brain metastasis; stereotactic radiosurgery; Ipilimumab; survival; safety; efficacy

Outcome Measures

Primary Outcomes (1)

• Overall survival rate

  until week 96 or death

Secondary Outcomes (6)

• All adverse events ≥ Grade 3 according to CTCAE, Version 4.0 criteria,

  through study completion, until week 96

• Overall response rate in brain

  until week 96 or death

• Global overall response rate

  until week 96 or death

• Disease control rate in brain

  until week 96 or death

• Global disease control rate

  until week 96 or death

Study Arms (1)

ipilimumab + Stereotactic Radiosurgery

EXPERIMENTAL

ipilimumab combined with a Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases

Drug: IPILIMUMAB; Radiation: Stereotactic radiosurgery

Interventions

IPILIMUMAB DRUG

ipilimumab + Stereotactic Radiosurgery

Stereotactic radiosurgery RADIATION

ipilimumab + Stereotactic Radiosurgery

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.
• Patient eligible to single dose Stereotactic Radiotherapy (Radiosurgery) as per the pluridisciplinary committee.
• Neurologically asymptomatic or pauci-symptomatic patients. Patients with moderated neurological symptoms without systemic corticosteroids treatment can be included.
• Less than 4 brain metastasis at the MRI. Brain metastasis should measure less than 3 cm in diameter. At least one brain metastasis \> 5mm.
• Maximum one prior systemic therapy for metastatic disease is allowed.
• Prior treatment with INTERFERON in the adjuvant setting is authorized. Prior treatment with anti-CTLA-4 is NOT authorized.
• ECOG Performance Status 0 or 1
• Within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified:

You may not qualify if:

• Neurological symptoms treated with systemic corticosteroids (whatever the dose of corticoids).
• 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.
• Any symptom of concomitant tumour meningitis
• History of immediate or delayed gadolinium hypersensitivity, or any contraindication to undergo MRI examination (Pacemaker, brain aneurysms clips)
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix (Subjects with a previous malignancy but without evidence of disease for 5 years will be allowed to enter the study)
• Uncontrolled infectious diseases - requires negative tests for clinically suspected HIV, HBV and 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. 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 motor neuropathy considered of autoimmune origin (e.g., Guillain Barré Syndrome) are excluded from this study
• Previous treatment with a CTLA-4 antagonist agent, including treatment in adjuvant setting.
• 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.
• For female patients: the patient is pregnant or lactating.
• Women of childbearing potential: refusal or inability to use effective means of contraception
• Participation in another clinical trial protocol within 30 days prior to enrolment
• Persons protected by a legal regime (guardianship, trusteeship)

Sponsors & Collaborators

• University Hospital, Lille: lead
• Bristol-Myers Squibb: collaborator

Study Sites (18)

CHU de Bordeaux

Bordeaux, France

Location

CHU de Caen

Caen, France

Location

Hôpital Trousseau - CHRU de Tours

Chambray-lès-Tours, France

Location

CHU - Hôpital d'Estaing

Clermont-Ferrand, France

Location

Hôpital A. Michallon

La Tronche, France

Location

CHRU, Hôpital Claude Huriez

Lille, France

Location

AP-HM Hôpital de la Timone

Marseille, France

Location

Hôpital Saint Eloi

Montpellier, France

Location

CHU Nantes - Place Alexis Ricordeau

Nantes, France

Location

Hôpital Archet 2

Nice, France

Location

AP-HP, Hôpital Ambroise Paré

Paris, France

Location

AP-HP, Hôpital Saint-Louis

Paris, France

Location

CHU de Bordeaux

Pessac, France

Location

Centre hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre Régional de Lutte Contre le Cancer Eugène Marquis

Rennes, France

Location

CHU de Toulouse - Larrey

Toulouse, France

Location

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, France

Location

Institut Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Ipilimumab; Radiosurgery

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Laurent Mortier, MD, PhD

  University Hospital, Lille

  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: January 20, 2016
• First Posted: January 25, 2016
• Study Start: September 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 25, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)