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

Melanoma Clinical Trial

— IPI+RTS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02662725
• Other study ID #: 2011_48
• Secondary ID: 2012-000852-32
• Status: Completed
• Phase: Phase 2
• First received: January 20, 2016
• Last updated: January 22, 2016
• Start date: September 2012
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Metastasis
• Brain Neoplasms
• Melanoma
• Neoplasm Metastasis

Intervention

Drug:
• IPILIMUMAB

Radiation:
• Stereotactic radiosurgery

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Bristol-Myers Squibb

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival rate		until week 96 or death	No
Secondary	All adverse events = Grade 3 according to CTCAE, Version 4.0 criteria,		through study completion, until week 96	Yes
Secondary	Overall response rate in brain	according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesion	until week 96 or death	No
Secondary	Global overall response rate	according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesions	until week 96 or death	No
Secondary	Disease control rate in brain	according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesions	until week 96 or death	No
Secondary	Global disease control rate	according to immune-related response criteria (ir-RC) and the mWHO criteria of target lesions	until week 96 or death	No
Secondary	Progression free survival		until week 96 or death	No