Ipilimumab Combined With a Stereotactic Radiosurgery in Melanoma Patients With Brain Metastases (IPI+RTS)

January 22, 2016 updated by: University Hospital, Lille

A Multicenter Phase II Study of Ipilimumab Combined With a Stereotactic Radiosurgery in Melanoma Patients With Brain Metastases

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

73

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France
        • CHU de Bordeaux
      • Caen, France
        • CHU de Caen
      • Chambray-lès-Tours, France
        • Hôpital Trousseau - CHRU de Tours
      • Clermont - Ferrand, France
        • CHU - Hôpital d'Estaing
      • La Tronche, France
        • Hôpital A. MICHALLON
      • Lille, France
        • CHRU, Hôpital Claude HURIEZ
      • Marseille, France
        • AP-HM Hopital de la Timone
      • Montpellier, France
        • Hopital Saint Eloi
      • Nantes, France
        • CHU Nantes - Place Alexis Ricordeau
      • Nice, France
        • Hôpital Archet 2
      • Paris, France
        • AP-HP, Hôpital Saint-Louis
      • Paris, France
        • AP-HP, Hôpital Ambroise Paré
      • Pessac, France
        • CHU de Bordeaux
      • Pierre-benite, France
        • Centre Hospitalier Lyon Sud
      • Rennes, France
        • Centre Régional de Lutte Contre le Cancer Eugène Marquis
      • Toulouse, France
        • CHU de Toulouse - Larrey
      • Vandoeuvre Les Nancy, France
        • Hôpitaux de Brabois
      • Villejuif, France
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Willing and able to give written informed consent.
  2. Men and women ≥ 18 years of age.
  3. Patient eligible to single dose Stereotactic Radiotherapy (Radiosurgery) as per the pluridisciplinary committee.
  4. Neurologically asymptomatic or pauci-symptomatic patients. Patients with moderated neurological symptoms without systemic corticosteroids treatment can be included.
  5. Less than 4 brain metastasis at the MRI. Brain metastasis should measure less than 3 cm in diameter. At least one brain metastasis > 5mm.
  6. Maximum one prior systemic therapy for metastatic disease is allowed.
  7. Prior treatment with INTERFERON in the adjuvant setting is authorized. Prior treatment with anti-CTLA-4 is NOT authorized.
  8. ECOG Performance Status 0 or 1
  9. Within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified:

Exclusion Criteria:

  1. The patient requires concomitant chronic treatment with systemic corticosteroids or any other immunosuppressive agents 7 days prior to inclusion.
  2. Neurological symptoms treated with systemic corticosteroids (whatever the dose of corticoids).
  3. 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.
  4. Any symptom of concomitant tumour meningitis
  5. History of immediate or delayed gadolinium hypersensitivity, or any contraindication to undergo MRI examination (Pacemaker, brain aneurysms clips)
  6. 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)
  7. 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.
  8. 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]).
  9. Subjects with motor neuropathy considered of autoimmune origin (e.g., Guillain Barré Syndrome) are excluded from this study
  10. Previous treatment with a CTLA-4 antagonist agent, including treatment in adjuvant setting.
  11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
  12. Lack of availability for clinical follow-up assessments.
  13. For female patients: the patient is pregnant or lactating.
  14. Women of childbearing potential: refusal or inability to use effective means of contraception
  15. Participation in another clinical trial protocol within 30 days prior to enrolment
  16. Persons protected by a legal regime (guardianship, trusteeship)
  17. Patients in emergency situations
  18. Patients kept in detention

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ipilimumab + Stereotactic Radiosurgery
ipilimumab combined with a Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases
Drug: IPILIMUMAB
Radiation: Stereotactic radiosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival rate
Time Frame: until week 96 or death
until week 96 or death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All adverse events ≥ Grade 3 according to CTCAE, Version 4.0 criteria,
Time Frame: through study completion, until week 96
through study completion, until week 96
Overall response rate in brain
Time Frame: until week 96 or death
according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesion
until week 96 or death
Global overall response rate
Time Frame: until week 96 or death
according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesions
until week 96 or death
Disease control rate in brain
Time Frame: until week 96 or death
according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesions
until week 96 or death
Global disease control rate
Time Frame: until week 96 or death
according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesions
until week 96 or death
Progression free survival
Time Frame: until week 96 or death
until week 96 or death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Collaborators

Bristol-Myers Squibb

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

January 20, 2016

First Submitted That Met QC Criteria

January 22, 2016

First Posted (Estimate)

January 25, 2016

Study Record Updates

Last Update Posted (Estimate)

January 25, 2016

Last Update Submitted That Met QC Criteria

January 22, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011_48
  • 2012-000852-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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