NCT01950195

Brief Summary

This research is being done to look at the safety of using stereotactic radiosurgery (SRS) and Ipilimumab together to treat melanoma that has spread to the brain or spine. Both Ipilimumab and SRS are used alone for the treatment of melanoma that has spread. Standard of care uses both of these treatments but not together. By using them together, we expect better treatment of melanoma, but there might be an increase in side effects. "Ipilimumab" is approved by the Food and Drug Administration (FDA) for the treatment of melanoma that has spread throughout the body. It works by activating your immune system to fight off cancer. "Stereotactic radiosurgery" (SRS) is approved by the Food and Drug Administration (FDA) for the treatment of melanoma in the brain or spine. It uses radiation to treat tumors without needing to cut or use stitches. The use of combining SRS and Ipilimumab in this research study is investigational. The word "investigational" means that this combination is not approved for marketing by the Food and Drug Administration but is allowed for use in this research study.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4

participants targeted

Target at below P25 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 21, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
24 days until next milestone

First Posted

Study publicly available on registry

September 25, 2013

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
Last Updated

November 15, 2016

Status Verified

November 1, 2016

Enrollment Period

3 years

First QC Date

June 21, 2013

Last Update Submit

November 10, 2016

Conditions

Keywords

MelanomaMetastasesBrainSpineSRS(Stereotactic Radiosurgery))Ipilimumab

Outcome Measures

Primary Outcomes (1)

  • Number of adverse events and severity of the adverse events.

    To assess the safety profile of stereotactic radiosurgery with ipilimumab in combination to treat patients with newly diagnosed melanoma brain or spinal metastases.

    2 years

Secondary Outcomes (1)

  • To estimate local control rate in brain and spine

    1 years

Other Outcomes (1)

  • Correlative Objective

    3 years

Study Arms (2)

Brain

EXPERIMENTAL

A cohort of six (6) patients will be treated at Dosing Schedule 1. If the observed dose limiting toxicity (DLT) rate is less ≤33%, the dose cohort will be expended to a total of 15 patients. Brain and spine metastases will be evaluated as two separate cohorts. If the first schedule produces DLTs in \>33% of patients, the Second Dosing schedule will be implemented. If the second dosing schedule produces DLTs in \>33% of patients, the Third Dosing schedule will be implemented. After 6 patients were enrolled in a cohort, their safety and toxicity will be continuously monitored till 12 weeks (3 months) after the initial dose of Ipilimumab is given for evaluating dose-limiting toxicities.

Procedure: Stereotactic Radiosurgery (SRS)Biological: Ipilimumab

Spine

EXPERIMENTAL

A cohort of six (6) patients will be treated at Dosing Schedule 1. If the observed dose limiting toxicity (DLT) rate is less ≤33%, the dose cohort will be expended to a total of 15 patients. Brain and spine metastases will be evaluated as two separate cohorts. If the first schedule produces DLTs in \>33% of patients, the Second Dosing schedule will be implemented. If the second dosing schedule produces DLTs in \>33% of patients, the Third Dosing schedule will be implemented. After 6 patients were enrolled in a cohort, their safety and toxicity will be continuously monitored till 12 weeks (3 months) after the initial dose of Ipilimumab is given for evaluating dose-limiting toxicities.

Procedure: Stereotactic Radiosurgery (SRS)Biological: Ipilimumab

Interventions

IpilimumabBIOLOGICAL
BrainSpine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have histologically confirmed diagnosis of melanoma. The pathologic confirmation may be from another metastatic site or from metastatic brain or spine lesions.
  • Patients must have Stage IV melanoma, with newly identified brain or spine metastases.
  • Patients must have measurable lesion in the brain or spine that is \> 3 mm seen on magnetic resonance imaging (MRI) with contrast.
  • NOTE: Contrasted pre-treatment MRI scan must be obtained ≤ 21 days prior to stereotactic radiosurgery treatment.
  • Karnofsky Performance Scale \>70%
  • Patients must have normal organ and marrow function as defined below:
  • leukocytes \>3,000/mcL absolute neutrophil count \>1,500/mcL platelets \>100,000/mcL total bilirubin ≤2X institutional upper limit of normal AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal creatinine within normal institutional limits OR According to Johns Hopkins MRI policy
  • Women of child bearing potential (WOCBP) using a reliable form of contraception during the study treatment period and for up to 12 weeks following the last dose of study drug \[21\].
  • Men must agree to the use of male contraception during the study treatment period and for at least 12 weeks after the last dose of study drug.
  • Ability to understand and the willingness to sign written informed consent document(s).

You may not qualify if:

  • Prior whole brain radiation or conventional radiation to the spine at the site of new lesion.
  • Prior chemotherapy within 28 days of starting treatment.
  • Prior therapy with investigational drugs within 28 days or at least 5 half-lives (whichever is longer) before study administration.
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody.
  • Neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Known allergy to compounds of similar chemical or biologic composition to ipilimumab.
  • Pregnant or breastfeeding women.
  • Known history of Human Immunodeficiency Virus.
  • Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) \[11\].
  • Active autoimmune disease, history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications. Exceptions include those with vitiligo or resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study \[11\].
  • Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up to 4 weeks (28 days) before receiving ipilimumab.
  • Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
  • Patients with both brain and spine metastases will be excluded from the trial.
  • Patients who are allergic to MRI contrast agent or have contraindication for MRI.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

MelanomaNeoplasm Metastasis

Interventions

RadiosurgeryIpilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RadiotherapyTherapeuticsStereotaxic TechniquesNeurosurgical ProceduresSurgical Procedures, OperativeInvestigative TechniquesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Michael Lim, MD

    Johns Hopkins Department of Neurosurgery

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 21, 2013

First Posted

September 25, 2013

Study Start

September 1, 2013

Primary Completion

September 1, 2016

Last Updated

November 15, 2016

Record last verified: 2016-11

Locations