Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery

NCT02097732 | Terminated Phase 2 Results DMC

• 2 other identifiers: UMCC 2013.114HUM00082134
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Melanoma; Brain Metastases

Keywords

Metastatic melanoma; Brain metastases; Radiation therapy; Immune therapy

Outcome Measures

Primary Outcomes (1)

• Local Control Rate

  The number of patients in each arm who are free from progression in the index (radiated) lesions in the brain at 6 months. Immune related response criteria was used to assess response to treatment. Immune-related Progressive Disease (irPD) in this trial is defined as an increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented.

  6 months

Secondary Outcomes (4)

• Overall Survival Rate

  Up to 5 years

• Regional (Intracranial) Control Rate

  6 months

• Intracranial Response Rate

  Up to 12 months

• Time to Progression

  From date of enrollment to up to 2 years

Other Outcomes (2)

• Imaging Correlates on Dynamic-contrast Enhanced MRI of the Brain

  6 months

• Immune Correlates

  6 months

Study Arms (2)

B: No induction

ACTIVE COMPARATOR

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.

Drug: Ipilimumab; Procedure: Stereotactic Radiosurgery

A: Induction

EXPERIMENTAL

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.

Drug: Ipilimumab; Procedure: Stereotactic Radiosurgery

Interventions

Ipilimumab DRUG

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

A: Induction; B: No induction

Stereotactic Radiosurgery 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; B: No induction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

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

Limitations and Caveats

Study halted prematurely due to a change in the standard of care treatment.

Results Point of Contact

• Title: Dr. Christopher Lao, MD, MPH
• Organization: University of Michigan Comprehensive Cancer Center

clao@med.umich.edu

(734) 936-4498

Study Officials

• Christopher Lao, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2014
• First Posted: March 27, 2014
• Study Start: April 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: July 1, 2020
• Last Updated: May 12, 2021
• Results First Posted: January 19, 2018

Record last verified: 2021-04

Locations

US (1)