Clinical trial NCT02097732: Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
Official title: Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Melanoma
Brain Metastases
Keywords: Metastatic melanoma
Brain metastases
Radiation therapy
Immune therapy
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2014-03-27
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study to test the efficacy of using standard immune therapy for melanoma prior to stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery followed by immune therapy. The study's hypothesis is that ipilimumab induction is as good as or better than controlling brain metastases as compared to stereotactic radiosurgery followed by immune therapy.

Detailed description: This is a randomized Phase II selection study investigating the use of ipilimumab induction prior to stereotactic radiosurgery (SRS), versus no induction, for melanoma brain metastases. Participants will be randomized to Arm A "Induction" (two doses of ipilimumab prior to SRS, two doses of ipilimumab after SRS) versus Arm B "No induction" (SRS first, followed by 4 doses of ipilimumab). Participants will undergo multiple dynamic contrast-enhanced MRIs of the brain and submit blood samples for immune testing.

Eligibility criteria: Inclusion Criteria:

* Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases
* At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm (Prior craniotomy and surgical resection is allowed, as long as there is at least one remaining measurable lesion in the brain)
* Patients must be candidates for stereotactic radiosurgery (SRS) and planning to undergo SRS
* Patients must be candidates for ipilimumab as determined by the treating physician
* Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
* At least 3 weeks has elapsed from any prior therapy, and the patient has recovered from side effects to ≤ grade 1 toxicities per Common Terminology Criteria (CTC) for Adverse Events
* Age \> or = 18 years old
* Performance status of ECOG of 0 or 1 (ECOG is the Eastern Oncology Cooperative Group Scoring system used to quantify cancer patients' general well-being and activities of daily life; scores range from 0 to 5 where 0 is perfect health and 5 is death)
* Adequate organ and marrow function: alanine aminotransferase (ALT ) \< 2.5x's upper limit of normal (ULN) of the institutional normal reference range, aspartate aminotransferase (AST) \< 2.5x's ULN of the institutional normal reference range, Bilirubin \< 1.5x's ULN of the institutional normal reference range, Creatinine \< 2.0 milligrams per deciliter, Platelets \> 50,000 per microliter
* Women of child-bearing potential must agree to use adequate contraception, defined as complete abstinence from intercourse with men or two methods
* Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

* Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index lesion(s) is in a different, non-contiguous location than the previously treated lesion.
* Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors are excluded due to the potential of effects on primary outcome
* Patients who require WBRT or surgery at the time of enrollment
* Neurologic symptoms or imaging findings that necessitate the use of steroids on the day of enrollment or in the prior 7 days
* Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice
* Concurrent treatment with any other anti-neoplastic drug or concurrent participation in another therapeutic clinical trial
* Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, history of allergic reaction/hypersensitivity to gadolinium)
* Women who are pregnant or are nursing
* Patients with absolute lymphocyte count of \<500 cells/microliter, who are known to be HIV positive, who have clinically significant active autoimmune disease, or are receiving immunosuppression following solid organ or stem cell transplant

Primary outcomes:
measure: Local Control Rate
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: Up to 5 years
measure: Regional (Intracranial) Control Rate
timeFrame: 6 months
measure: Intracranial Response Rate
timeFrame: Up to 12 months
measure: Time to Progression
timeFrame: From date of enrollment to up to 2 years
Other outcomes:
measure: Imaging Correlates on Dynamic-contrast Enhanced MRI of the Brain
timeFrame: 6 months
measure: Immune Correlates
timeFrame: 6 months
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Christopher Lao, M.D.
role: PRINCIPAL_INVESTIGATOR
References: