Clinical Trials /

SRS and Nivolumab in Treating Patients With Newly Diagnosed Melanoma Metastases in the Brain or Spine

NCT02716948

Description:

This phase I pilot trial studies the side effects of stereotactic radiosurgery and nivolumab in treating patients with newly diagnosed melanoma that has spread to the brain or spine. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor to more precisely target the cancer. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving stereotactic radiosurgery together with nivolumab may be a better treatment for melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SRS and Nivolumab in Treating Patients With Newly Diagnosed Melanoma Metastases in the Brain or Spine
  • Official Title: A Pilot Study of Stereotactic Radiosurgery Combined With Nivolumab in Patients With Newly Diagnosed Melanoma Metastases in the Brain and Spine

Clinical Trial IDs

  • ORG STUDY ID: J15214
  • SECONDARY ID: NCI-2016-00370
  • SECONDARY ID: IRB00086553
  • NCT ID: NCT02716948

Conditions

  • Metastatic Malignant Neoplasm in the Brain
  • Metastatic Malignant Neoplasm in the Spine
  • Stage IV Skin Melanoma

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, ONO-4538, OpdivoTreatment (nivolumab, stereotactic radiosurgery)

Purpose

This phase I pilot trial studies the side effects of stereotactic radiosurgery and nivolumab in treating patients with newly diagnosed melanoma that has spread to the brain or spine. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor to more precisely target the cancer. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving stereotactic radiosurgery together with nivolumab may be a better treatment for melanoma.

Detailed Description

      PRIMARY OBJECTIVES:

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

      SECONDARY OBJECTIVES:

      I. To estimate local control rate in brain and spine. II. To estimate systematic control
      rate. III. To estimate progression-free survival.

      TERTIARY OBJECTIVES:

      I. To explore peripheral blood immune response during and after treatment.

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Patients then
      undergo stereotactic radiosurgery on day 8 per standard of care. Courses with nivolumab
      repeats every 14 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, every 10 weeks,
      and then every 3 months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, stereotactic radiosurgery)ExperimentalPatients receive nivolumab IV over 60 minutes on day 1. Patients then undergo stereotactic radiosurgery on day 8 per standard of care. Courses with nivolumab repeats every 14 days in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  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%
    
              -  Leukocytes >= 3,000/mcL
    
              -  Absolute neutrophil count >= 1,500/mcL
    
              -  Platelets >= 100,000/mcL
    
              -  Total bilirubin =< 2 x institutional upper limit of normal
    
              -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/
                 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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) must use a reliable form of contraception
                 during the study treatment period and for up to 12 weeks following the last dose of
                 study drug
    
              -  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)
    
            Exclusion Criteria:
    
              -  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- programmed cell death 1 (PD-1), anti- programmed cell
                 death-ligand 1 (PD-L1), or anti-PDL-2 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 nivolumab
    
              -  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)
    
              -  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
    
              -  Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up
                 to 4 weeks (28 days) before receiving nivolumab
    
              -  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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of serious adverse events (SAE) graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.0
    Time Frame:Up 12 weeks after first dose of study treatment
    Safety Issue:
    Description:All SAEs will be tabulated by type and grade. Proportion of individual type of SAE event will be estimated using the binomial distribution along with 95% confidence interval (exact method).

    Secondary Outcome Measures

    Measure:Changes in the immune profile of peripheral blood during and after treatment with nivolumab in combination with stereotactic radiosurgery (immune response)
    Time Frame:Baseline to up to 12 months
    Safety Issue:
    Description:Correlative outcomes will be summarized using descriptive statistics. Logistic regression model will be considered to explore potential association between the control rate and correlative outcomes.
    Measure:Incidence of toxicity graded according to the NCI CTC 4.0
    Time Frame:Up to 30 days after completion of study treatment
    Safety Issue:
    Description:Toxicity events will be tabulated by type and grade. The severity and frequency of the toxicity will be tabulated by the tested dose or doses using descriptive statistics. The proportions of patient who experienced grade 3 or above toxicities will be estimated, along with 95% confidence intervals by each type of toxicity.
    Measure:Local control rate in brain defined as no change in number of lesions at initial treatment in the brain and change on size of targeted lesion is =< 25% from initial measurement
    Time Frame:From date of initial nivolumab treatment to first date that progressive disease is objectively documented, assessed up to 3 years
    Safety Issue:
    Description:The local control rate will be estimated using binomial distribution along with 95% confidence. The duration of the local control will be summarized using median and range.
    Measure:Progression-free survival according to Response Evaluation Criteria in Solid Tumors criteria 1.1
    Time Frame:From the date of initial diagnosis (at surgery) to the date of progressive disease was defined (documented), assessed up to 3 years
    Safety Issue:
    Description:The probability of progression-free survival will be estimated using the Kaplan-Meier method.
    Measure:Systematic control rate in spine defined as no change in number of lesions at initial treatment in the spine and change on size of targeted lesion is =< 25% from initial measurement
    Time Frame:Up to 3 years
    Safety Issue:
    Description:The systematic control rate will be estimated using binomial distribution along with 95% confidence.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center

    Last Updated

    November 10, 2016