Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02716948
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
Accuray Incorporated
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Malignant Neoplasm in the Brain Metastatic Malignant Neoplasm in the Spine Stage IV Skin Melanoma Other: Laboratory Biomarker Analysis Biological: Nivolumab Radiation: Stereotactic Radiosurgery Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Stereotactic Radiosurgery Combined With Nivolumab in Patients With Newly Diagnosed Melanoma Metastases in the Brain and Spine
Actual Study Start Date : June 23, 2016
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Treatment (nivolumab, stereotactic radiosurgery)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • ONO-4538
  • Opdivo

Radiation: Stereotactic Radiosurgery
Undergo stereotactic radiosurgery
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiation Therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery




Primary Outcome Measures :
  1. 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 ]
    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 :
  1. 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 ]
    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.

  2. Incidence of toxicity graded according to the NCI CTC 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]
    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.

  3. 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 ]
    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.

  4. 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 ]
    The probability of progression-free survival will be estimated using the Kaplan-Meier method.

  5. 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 ]
    The systematic control rate will be estimated using binomial distribution along with 95% confidence.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02716948


Contacts
Layout table for location contacts
Contact: Kelly Szajna, RN, BSN 410-502-4081 kszajna1@jhmi.edu
Contact: Whitney Webb, RN, MSN 410-955-7008 wwebb10@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Michael K. Lim    410-614-1627    mlim3@jhmi.edu   
Principal Investigator: Michael K. Lim         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Accuray Incorporated
Investigators
Layout table for investigator information
Principal Investigator: Michael Lim Johns Hopkins University/Sidney Kimmel Cancer Center

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02716948    
Other Study ID Numbers: J15214
NCI-2016-00370 ( Registry Identifier: CTRP )
IRB00086553 ( Other Identifier: JHMIRB )
First Posted: March 23, 2016    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms, Second Primary
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Melanoma
Nevi and Melanomas
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents