Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery

NCT ID: NCT02097732

Last Updated: 2021-05-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2020-07-31

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.

Conditions

Metastatic Melanoma; Brain Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

B: No induction

Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses.

Group Type: ACTIVE_COMPARATOR

Ipilimumab

Intervention Type: DRUG

Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.

Stereotactic Radiosurgery

Intervention Type: PROCEDURE

Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.

A: Induction

Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses.

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: DRUG

Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.

Stereotactic Radiosurgery

Intervention Type: PROCEDURE

Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.

Interventions

Ipilimumab

Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.

Intervention Type: DRUG

Stereotactic Radiosurgery

Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Lao, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

University of Michigan Hospital

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

HUM00082134

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2013.114

Identifier Type: -

Identifier Source: org_study_id