Stereotactic Radiosurgery and Immune Checkpoint Inhibitors With NovoTTF-200M for the Treatment of Melanoma Brain Metastases

NCT05341349 | Terminated Phase 1 DMC FDA Device

• 4 other identifiers: STUDY00003588NCI-2021-05980RAD5236-21P30CA138292
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial finds out the side effects and possible benefits of stereotactic radiosurgery and immune checkpoint inhibitors with NovoTTF-100M for the treating of melanoma that has spread to the brain (brain metastases). Stereotactic radiosurgery is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. NovoTTF-100M is a portable battery operated device which produces tumor treating fields in the body by means of surface electrodes placed on the skin. Tumor treating fields are low intensity, intermediate frequency electric fields that pulse through the skin to disrupt cancer cells' ability to divide. Giving stereotactic radiosurgery and immune checkpoint inhibitors with NovoTTF-100M may work better than stereotactic radiosurgery and immune checkpoint inhibitors.

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8; Melanoma of Unknown Primary; Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Metastatic Mucosal Melanoma; Metastatic Ocular Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• The percentage of patients developing grade 3 CNS toxicity

  Will be analyzed separately for arms 1 and 2. Radiation Therapy Oncology Group Grade 3 CNS toxicity will be measured using RTOG grade 3 CNS toxicity and reported as percentage of patients developing grad 3 CNS toxicity. Higher score means more patients developing toxicity. Lower score means less patients developing toxicity.

  At 3 months

Secondary Outcomes (6)

• Rates of skin toxicity

  At 4-6 weeks and 3 months

• Rates of alopecia

  At 4-6 weeks and 3 months

• Time to progression

  At 6 and 12 months

• Intracranial control

  At 6 and 12 months

• Progression free survival (PFS)

  From SRS to disease progression or death, assessed up to 2 years

Study Arms (2)

Arm I (SRS, pembrolizumab, TTFields)

EXPERIMENTAL

Patients receive standard of care pembrolizumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Radiation: Stereotactic Radiosurgery; Procedure: Tumor Treating Fields Therapy

Arm II (nivolumab, ipilimumab, SRS, TTFields)

EXPERIMENTAL

Patients receive standard of care nivolumab and ipilimumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab; Radiation: Stereotactic Radiosurgery; Procedure: Tumor Treating Fields Therapy

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Arm II (nivolumab, ipilimumab, SRS, TTFields)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Arm II (nivolumab, ipilimumab, SRS, TTFields)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm I (SRS, pembrolizumab, TTFields)

Stereotactic Radiosurgery RADIATION

Undergo SRS

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

Arm I (SRS, pembrolizumab, TTFields); Arm II (nivolumab, ipilimumab, SRS, TTFields)

Tumor Treating Fields Therapy PROCEDURE

Undergo TTFields

Also known as: Alternating Electric Field Therapy, TTF, TTFields

Arm I (SRS, pembrolizumab, TTFields); Arm II (nivolumab, ipilimumab, SRS, TTFields)

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial
• Have diagnosis of malignant melanoma.
• Be \>= 22 years of age on the day of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 or Karnofsky performance status \>= 70%
• Patients must have histological diagnosis of melanoma
• Preference is for treatment naive patients that have not gotten previous immunotherapy. However, if approved by principal investigator (PI), patients that have gotten prior PD1 and/or dual immune checkpoint inhibitor therapy may be allowed on this trial if they have progressed intra-cranially or extra-cranially, and have very limited disease progression.
• Patient must be asymptomatic at time of getting SRS (day 0) on trial. Prednisone =\< 20 mg/day (4 mg or less of dexamethasone equivalent) for at least 7 days prior to treatment is allowed
• Patients with ocular, mucosal and unknown primary melanoma will also be eligible
• Patients with 1-10 untreated brain metastases at time of initial brain metastases diagnosis (surgery to at least one of the brain lesions and/or biopsy of a lesion for diagnostic purposes and/or for standard of care purposes is acceptable). If patient has surgical removal of at least one lesion, the investigator would wait for a reasonable time after surgery to start the TTFields, SRS and Immunotherapy. This is typically around 2-4 weeks after resection and clearance by neurosurgery to start the treatment. However, the exact time to start would depend on institutional standard of care practice pattern. Enrollment of patient can take place before or after planned surgery.
• Eligible for hypofractionation approach (9 Gy x 3 or 6 Gy x 5). 9 Gyx 3 is preferred approach, but 6 Gy x 5 fractions is acceptable
• Eligible for immunotherapy and TTFields. The TTField wires will be removed immediately before the SRS delivery and then reconnected again immediately after SRS each session. The arrays will be left on the skin during SRS. This is to minimize any electrical discharge from the wires that may occur as a result of SRS beams going through the arrays and/or lead to any dose heterogeneity during SRS delivery and/or damage the electrical, battery operated equipment
• Be willing to comply with NovoTTF-100M device treatment for at least 75% of the time
• Must have caregiver or self support available to assist transducer array exchange.
• Prior radiation to the primary and/or regional radiotherapy for melanoma is acceptable.
• Baseline labs as within standard of care (complete blood count \[CBC\], comprehensive metabolic panel \[CMP\], lactate dehydrogenase \[LDH\], erythrocyte sedimentation rate \[ESR\], etc) are required within 28 days of enrollment.

You may not qualify if:

• Implanted electrical device (TTField is not implanted device, but worn externally)
• Sensitive to gel used with electrocardiogram (ECG), electrical nerve stimulation, contact with gel used with Novo-TTF system
• Has a diagnosis of immunodeficiency or is receiving systemic steroids (less than or equal to 20 mg prednisone equivalent or less than 4 mg dexamethasone per day at time of start of treatment is ok) therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• If they have brain metastases located in the brain stem (including midbrain, pons, or medulla)
• Inability to undergo MRI evaluation for treatment planning and follow-up
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. Has a diagnosis of immunodeficiency or is receiving systemic steroids (less than or equal to 20 mg prednisone equivalent or 4 mg dexamethasone at time of start of treatment is ok) therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab, ipilimumab or any of its recipients
• Hypersensitivity to hydrogel (needed for TTFields)
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of (non-infectious) pneumonitis that required steroids (less than or equal to 20 mg prednisone equivalent at time of start of treatment is ok) or current pneumonitis

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• NovoCure Ltd.: collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Melanoma; Uveal Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; pembrolizumab; 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; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mohammad K Khan, MD, PhD

  Emory University Hospital/Winship Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 11, 2022
• First Posted: April 22, 2022
• Study Start: October 13, 2022
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)