Melanoma With Brain MetastasisPhase 2NCT03903640
Optune Device - TT Field Plus Nivolumab and Ipilimumab for Melanoma With Brain Metastasis
A Phase 2 study testing Optune, Nivolumab and Ipilimumab in people with Melanoma With Brain Metastasis, run by Washington University School of Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma With Brain Metastasis
- What is being tested?
- Optune, Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2019to 3 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: 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.
- Conditions
- Melanoma With Brain Metastasis
- Being tested
- Optune, Nivolumab, Ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OptuneDevice
-Optune is programmed by Novocure to deliver 200 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 707mARMS.
NivolumabBiological
Also called Opdivo
-Standard of care
IpilimumabBiological
Also called Yervoy
-Standard of care
| Study group | Role | What they receive |
|---|---|---|
| Optune + Ipilimumab + Nivolumab | Experimental | * 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 Receives: Device: Optune; Biological: Nivolumab; Biological: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At 6 months (up to 184 days)
Secondary outcomes (6)
Overall Survival
-Defined as the duration of time from the date of first dose of study treatment to death from any cause.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: Through 100 days after completion of treatment (median follow-up 107.5 days, full range (25 days-190 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start14 Oct 2019
- Primary completion8 Jun 2020
- Study completion3 Nov 2021
Why it stopped: The study was terminated early on 03/09/2022 due to low accrual during the COVID-19 pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Melanoma With Brain MetastasisStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- NovoCure Ltd.
- Responsible party
- Sponsor
- Investigators
- George Ansstas, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03903640
- Sponsor's protocol ID
- 201903162
- Status last verified
- May 2022
- First submitted
- 3 Apr 2019
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Optune Device - TT Field Plus Nivolumab and Ipilimumab for Melanoma With Brain Metastasis
- ClinicalTrials.gov ID
- NCT03903640
- Acronym / sponsor ID
- 201903162
- Conditions
- Melanoma With Brain Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early on 03/09/2022 due to low accrual during the COVID-19 pandemic.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- NovoCure Ltd.
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 8 Jun 2020 (actual)
- Study completion
- 3 Nov 2021 (actual)
- First posted
- 4 Apr 2019 (actual)
- Results
- Posted 12 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Optune + Ipilimumab + Nivolumab | Experimental | Device: Optune, Biological: Nivolumab, Biological: Ipilimumab* 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Optune-Optune is programmed by Novocure to deliver 200 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 707mARMS. | Device | Optune + Ipilimumab + Nivolumab |
| NivolumabAlso: Opdivo-Standard of care | Biological | Optune + Ipilimumab + Nivolumab |
| IpilimumabAlso: Yervoy-Standard of care | Biological | Optune + Ipilimumab + Nivolumab |
Primary outcome
Intracranial Progression-free Survival
Time frame: At 6 months (up to 184 days)
* 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).
6 secondary outcomes
Overall Survival
Time frame: At 6 months (up to 184 days)
Best Intracranial Response Rate
Time frame: Until disease progression or death whichever comes first (median follow-up 53 days (full range 15-91 days))
Best Extracranial Response Rate
Time frame: Until disease progression or death whichever comes first (median follow-up 53 days (full range 15-91 days))
Extracranial Progression-free Survival
Time frame: At 6 months
Safety of the Treatment Regimen as Measured by Number of Participants With Treatment-related Grade 3 or Greater Adverse Events
Time frame: 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.
Time frame: Through 100 days after completion of treatment (median follow-up 107.5 days, full range (25 days-190 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Ansstas, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Optune, Nivolumab and Ipilimumab in people with Melanoma With Brain Metastasis, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracranial Progression-free Survival (time frame: At 6 months (up to 184 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2022.