Optune Device - TT Field Plus Nivolumab and Ipilimumab for Melanoma With Brain Metastasis

Phase II Study of Optune Device - TT Field Plus Nivolumab and Ipilimumab for Melanoma With Brain Metastasis

This phase II study will evaluate the safety of combining intermediate frequency electric field (TT Field) with immunotherapy in melanoma patients with brain metastasis. The data of this study will also inform whether this combination will offer advantage in progression free survival (PFS) and overall survival.

Study Overview

• Status: Terminated
• Conditions: Melanoma With Brain Metastasis
• Intervention / Treatment: Device: Optune; Biological: Nivolumab; Biological: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed melanoma with metastasis to the brain.
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Candidate for treatment with immunotherapy.
• At least 18 years of age.

• Normal bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Total bilirubin ≤ 1.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation, including at least 5 months (for women of childbearing potential) and at least 7 months (for men) after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Received treatment in the metastatic setting
• Treated with whole brain radiation Receiving targeted therapy or on immunosuppressive agents (dexamethasone> 4mg/day) within 1 week of therapy.
• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, ipilimumab, or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• History of pre-existing immunodeficiency disorder or autoimmune condition requiring immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
• Known sensitivity to conductive hydrogels.
• Skull defects such as missing bone or bullet fragments.
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, vagus nerve stimulator, and other implanted electronic devices in the brain or spinal cord.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with nivolumab and/or ipilimumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Optune + Ipilimumab + Nivolumab; Ipilimumab at 3 mg/kg IV over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.; Nivolumab at 1 mg/kg IV over 30 minutes on Day 1 of each 21-day cycle for 4 cycles, then at 240 mg IV over 30 minutes on Days 1 and 15 of each 28-day cycle for up to 20 doses; Within 2 weeks of the start of ipilimumab (before or after), treatment with Optune will begin. All patients will be required to shave their heads to initiate array placement and Optune therapy.; Treatment may continue for up to 1 year

Device: Optune; -Optune is programmed by Novocure to deliver 200 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 707mARMS.; Biological: Nivolumab; -Standard of care; Other Names: Opdivo; Biological: Ipilimumab; -Standard of care; Other Names: Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Progression-free Survival	The PFS time will be calculated as the duration of time from the date of first dose of study treatment to the date of earliest intracranial progression or death, whichever occurs first.; Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).	At 6 months (up to 184 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	-Defined as the duration of time from the date of first dose of study treatment to death from any cause.	At 6 months (up to 184 days)
Best Intracranial Response Rate	Defined as the percentage of patients with a confirmed intracranial complete or partial response; Using modified RANO criteria	Until disease progression or death whichever comes first (median follow-up 53 days (full range 15-91 days))
Best Extracranial Response Rate	Defined as the percentage of patients with a confirmed extracranial complete or partial response; Using modified RANO criteria	Until disease progression or death whichever comes first (median follow-up 53 days (full range 15-91 days))
Extracranial Progression-free Survival	Defined as the duration of time from the date of first dose of study treatment to the date of earliest extracranial progression or death, whichever occurs first. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up.; Using modified RANO criteria	At 6 months
Safety of the Treatment Regimen as Measured by Number of Participants With Treatment-related Grade 3 or Greater Adverse Events	-The descriptions and grading scales found in CTCAE version 5.0.	Through 100 days after completion of treatment (median follow-up 107.5 days, full range (25 days-190 days)
Safety of the Treatment Regimen as Measured by Number of Participants With Discontinuations Due to Treatment Related Adverse Events.	-The descriptions and grading scales found in CTCAE version 5.0.	Through 100 days after completion of treatment (median follow-up 107.5 days, full range (25 days-190 days)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: NovoCure Ltd.

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2019
• Primary Completion (ACTUAL): June 8, 2020
• Study Completion (ACTUAL): November 3, 2021

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 3, 2019
• First Posted (ACTUAL): April 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasm Metastasis; Brain Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: 201903162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No