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.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Nivolumab | Opdivo | Optune + Ipilimumab + Nivolumab |
| Ipilimumab | Yervoy | Optune + Ipilimumab + Nivolumab |
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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 |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Intracranial progression-free survival |
| Time Frame: | At 6 months |
| Safety Issue: | |
| Description: | 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. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up. 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). |
| Measure: | Overall survival |
| Time Frame: | At 6 months |
| Safety Issue: | |
| Description: | -Defined as the duration of time from the date of first dose of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up. |
| Measure: | Best intracranial response rate |
| Time Frame: | Until disease progression or death (up to 3 years after off-treatment date) |
| Safety Issue: | |
| Description: | Defined as the percentage of patients with a confirmed intracranial complete or partial response Using modified RANO criteria |
| Measure: | Best extracranial response rate |
| Time Frame: | Until disease progression or death (up to 3 years after off-treatment date) |
| Safety Issue: | |
| Description: | Defined as the percentage of patients with a confirmed extracranial complete or partial response Using modified RANO criteria |
| Measure: | Extracranial progression-free survival |
| Time Frame: | At 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Safety of the treatment regimen as measured by number of treatment-related grade 3 or greater adverse events and discontinuations due to treatment related adverse events. |
| Time Frame: | Through 100 days after completion of treatment (estimated to be 1 year and 100 days) |
| Safety Issue: | |
| Description: | -The descriptions and grading scales found in CTCAE version 5.0. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Washington University School of Medicine |
August 16, 2021
