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

NCT02716948 | Completed Phase 1 DMC

• 3 other identifiers: J15214NCI-2016-00370IRB00086553
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of serious adverse events (SAE) graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.0

  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).

  Up 12 weeks after first dose of study treatment

Secondary Outcomes (5)

• Changes in the immune profile of peripheral blood during and after treatment with nivolumab in combination with stereotactic radiosurgery (immune response)

  Baseline to up to 12 months

• Incidence of toxicity graded according to the NCI CTC 4.0

  Up to 30 days after completion of study treatment

• 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

  From date of initial nivolumab treatment to first date that progressive disease is objectively documented, assessed up to 3 years

• Progression-free survival according to Response Evaluation Criteria in Solid Tumors criteria 1.1

  From the date of initial diagnosis (at surgery) to the date of progressive disease was defined (documented), assessed up to 3 years

• 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

  Up to 3 years

Study Arms (1)

Treatment (nivolumab, stereotactic radiosurgery)

EXPERIMENTAL

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; Biological: Nivolumab; Radiation: Stereotactic Radiosurgery

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nivolumab, stereotactic radiosurgery)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, ONO-4538, Opdivo

Treatment (nivolumab, stereotactic radiosurgery)

Stereotactic Radiosurgery RADIATION

Undergo stereotactic radiosurgery

Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery

Treatment (nivolumab, stereotactic radiosurgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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%
• 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)

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- 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, e.g. organ, tissue, or allogenic hematopoietic stem cell transplant (HSCT) recipients. 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 live vaccines against infectious diseases up to 4 weeks (28 days) before receiving nivolumab. (NOTE: Inactivated seasonal influenza vaccines are permitted and do not require a 4-week waiting period before starting study treatment).
• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Accuray Incorporated: collaborator

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Melanoma

Interventions

Nivolumab; Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue 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

Study Officials

• Lawrence Kleinberg

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 23, 2016
• Study Start: June 23, 2016
• Primary Completion: August 27, 2021
• Study Completion: August 27, 2021
• Last Updated: November 30, 2021

Record last verified: 2021-11

Locations

US (1)