NovoTTF-200A + Pembrolizumab In Melanoma Brain Metastasis

NCT04129515 | Withdrawn Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: BrUOG 416
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This research study involves studying a device as a possible treatment for metastatic melanoma in the brain. The purpose of this study is to obtain information on the safety and effectiveness of the study device, NovoTTF-200A, in melanoma participants with brain metastases when it is combined with Pembrolizumab. The name of the study device involved in this study is: \-- NovoTTF-200A The name of the drug used in this study is: \-- Pembrolizumab

Conditions

Metastatic Melanoma; Melanoma Brain Metastasis

Keywords

Melanoma Brain Metastasis; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Dose Limiting Toxicity

  Dose limited toxicity is considered grade 3 or higher treatment-related adverse events.

  21 Days

Secondary Outcomes (4)

• Overall Response Rate

  defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 100 months

• 12-month Overall Survival Rate

  1 Year after last study treatment

• 6-month progression-free survival (PFS) rate

  6 months after last study treatment

• Quality of Life Assessment

  Baseline, 63 Days, 129 Days, 189 Days, 30 days after last study treatment

Study Arms (2)

PHASE 1: NovoTTF-200A + PEMBROLIZUMAB

EXPERIMENTAL

The Phase I portion of the study will have a 3 + 3 design and consist of one cohort treated * NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle. * Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Device: NovoTTF-200A; Drug: Pembrolizumab

PHASE 2: NovoTTF-200A + PEMBROLIZUMAB

EXPERIMENTAL

* NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle. * Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Device: NovoTTF-200A; Drug: Pembrolizumab

Interventions

NovoTTF-200A DEVICE

•NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle

PHASE 1: NovoTTF-200A + PEMBROLIZUMAB; PHASE 2: NovoTTF-200A + PEMBROLIZUMAB

Pembrolizumab DRUG

Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Also known as: Keytruda®

PHASE 1: NovoTTF-200A + PEMBROLIZUMAB; PHASE 2: NovoTTF-200A + PEMBROLIZUMAB

Eligibility Criteria

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

You may qualify if:

• For phase 1 portion: Participants must have histologically confirmed melanoma (either measurable or evaluable) that is metastatic to the brain (TNM classification: Any T, Any N and M1d with or without M1a or M1b involvement). Direct pathological confirmation of metastatic melanoma from the brain is not necessary, provided that the lesions on neuroimaging (either gadolinium-enhanced MRI (preferred) or contrast-enhanced CT of the head) possess typical characteristics of brain metastases as determined by the treating investigator. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm by MRI. Evaluable lesions are those that are \<10 mm in all dimensions. Both BRAF wild-type and mutated melanomas are eligible; BRAF mutated patients are required to have previously progressed on or not tolerate BRAF/MEK targeted therapy.
• For phase 2 portion: Participants must have histologically confirmed and measurable melanoma tumor that is metastatic to the brain (TNM classification: Any T, Any N and M1d with or without M1a or M1b involvement). Direct pathological confirmation of metastatic melanoma from the brain is not necessary, provided that the lesions on neuroimaging (either gadolinium-enhanced MRI (preferred) or contrast-enhanced CT of the head) possess typical characteristics of brain metastases as determined by the treating investigator. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm by MRI. Both BRAF wild-type and mutated melanomas are eligible; BRAF mutated patients are required to have previously progressed on or not tolerate BRAF/MEK targeted therapy.
• Age 18 or above.
• ECOG performance status 0-1 or Karnofsky ≥80 (see Appendix A)
• Life expectancy of greater than 6 months.
• Participants 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 within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 x institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• albumin \>2.5 mg/dL
• INR or PT ≤1.5 x ULN unless subject is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants)

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Subjects with newly diagnosed brain metastasis during checkpoint inhibitor treatment are eligible, as long as they have stable or regressing systemic melanoma and the only site of relapse is in the brain.
• Participants who are receiving any other investigational agents.
• History of hypersensitivity to pembrolizumab or any of its excipients.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women, or those expecting to conceive or father children within the projected duration of the trial (starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment), are excluded from this study.
• A diagnosis of immunodeficiency or HIV.
• A known history of active TB (Bacillus Tuberculosis)
• Systemic steroid therapy at a dose equivalent to 4 mg daily of dexamethasone or more, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Hypersensitivity to hydrogel.
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to the agents.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 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.
• 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.
• Known leptomeningeal metastasis. Confirmation of negative leptomeningeal metastasis, either by CSF analysis or by neuroimaging staging (no leptomeningeal enhancement or drop metastasis on gadolinium-enhanced head or total spine MRI, respectively) should be determined by the treating investigator. However, it is recommended that both CSF and neuroimaging be obtained because both modalities have limitations in sensitivity and specificity.
• Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of enlarging brain metastases, and are not using excessive steroids (defined as a dexamethasone dose of \>4 mg daily or equivalent) for at least 7 days prior to trial treatment. This exception does not include leptomeningeal metastasis, which is excluded regardless of clinical stability.
• 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). Pre-existing hypothyroidism and type I diabetes mellitus (including those from prior anti-cancer monoclonal antibody treatment) are not considered as active autoimmune diseases. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Sponsors & Collaborators

• Brown University: lead
• NovoCure Ltd.: collaborator

Study Sites (1)

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Eric T Wong, MD

  Lifespan 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: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 16, 2019
• Study Start: October 30, 2025
• Primary Completion: December 1, 2025
• Study Completion: January 1, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)