Clinical Trials /

NovoTTF-200A + Pembrolizumab In Melanoma Brain Metastasis

NCT04129515

Description:

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

Related Conditions:
  • Melanoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NovoTTF-200A + Pembrolizumab In Melanoma Brain Metastasis
  • Official Title: Phase I and II Study of NovoTTF-200A and Pembrolizumab in Newly Diagnosed Melanoma Brain Metastasis

Clinical Trial IDs

  • ORG STUDY ID: 18-615
  • NCT ID: NCT04129515

Conditions

  • Metastatic Melanoma
  • Melanoma Brain Metastasis

Interventions

DrugSynonymsArms
PembrolizumabKeytruda®PHASE 1: NovoTTF-200A + PEMBROLIZUMAB

Purpose

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

Detailed Description

      The research study procedures include screening for eligibility and study treatment including
      evaluations and follow up visits.

        -  The name of the study device involved in this study is: NovoTTF-200A

        -  The name of the drug used in this study is: Pembrolizumab

        -  Eligible participants will be in this research study for up to 2 years, or until
           progressive disease or unacceptable toxicity as is reflected in the protocol.

        -  This is a Phase I/II clinical trial.

             -  A Phase I clinical trial tests the safety and toxicity of adding an investigational
                device NovoTTF-200A to standard-of-care drug Pembrolizumab to use for further
                studies.

             -  A Phase II clinical trial tests how well the combination works for your brain
                disease. "Investigational" means that the device is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved NovoTTF-200A for your brain
      metastasis from melanoma.

      A metastatic brain tumor is usually found when a cancer patient begins to experience
      neurological symptoms and a brain scan (CT or MRI) is ordered. However, some participants are
      symptom-free and are only diagnosed with brain metastases with MRI or CT scans for another
      reason.

      The NovoTTF-200A System is a portable device which produces changing electrical fields,
      called Tumor Treatment Fields ("TTFields") within the human body. TTFields stop the growth of
      tumor cells resulting in cell death of the rapidly dividing cancer cells. TTFields may also
      sensitize the tumor cells to immune therapies and this is the rationale for combining
      NovoTTF-200A and Pembrolizumab.

      The system is a portable, light-weighted, battery operated device designed to deliver
      TTFields directly to the region where brain metastasis are. The device can be carried
      backpack while working or doing other activities of daily living.
    

Trial Arms

NameTypeDescriptionInterventions
PHASE 1: NovoTTF-200A + PEMBROLIZUMABExperimentalThe 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
  • Pembrolizumab
PHASE 2: NovoTTF-200A + PEMBROLIZUMABExperimentalNovoTTF-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
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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 measureable
             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

          -  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)

          -  aPTT ≤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) All screening labs
             should be performed within 14 days of treatment initiation. Screening labs can be used
             as treatment day labs when they are obtained within 3 days of Cycle 1 Day 1.

          -  Have either measurable or evaluable disease in Phase I & must have measurable disease
             in Phase II based on the RANO criteria for brain metastases (maximum tumor diameter is
             3 cm).

          -  Have at least 1 untreated brain metastasis for response assessment. Subjects with
             solitary melanoma brain metastasis should not be treated with either surgery or
             radiation prior to trial entry.

          -  Confirm available archival or newly obtained tissue (either brain or systemic) from
             prior core or excisional biopsy of a tumor lesion.

          -  Be willing to comply with NovoTTF-200A device treatment for at least 75% of the time.

          -  Must have caregiver or support available to assist transducer array exchange.

          -  Female subjects of childbearing potential should have a negative urine or serum
             pregnancy within 14 days (or within 72 hours if deemed necessary by the treating
             investigator) prior to receiving the first dose of study medication. If the urine test
             is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required.

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, use barrier methods of contraception, or abstain
             from heterosexual activity for the course of the study through 120 days after the last
             dose of study medication (Reference Section 5.8). Subjects of childbearing potential
             are those who have not been surgically sterilized or have not been free from menses
             for > 1 year.

          -  Male subjects should agree to use an adequate method of contraception, including
             spermicide, starting with the first dose of study therapy through 120 days after the
             last dose of study therapy.

          -  The effects of NovoTTF-200A and pembrolizumab on the developing human fetus are
             unknown. For this reason, women of child-bearing 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. Should a woman become
             pregnant or suspect she is pregnant while she or her partner is participating in this
             study, she should inform her treating physician immediately. Men treated or enrolled
             on this protocol must also agree to use adequate contraception prior to the study, for
             the duration of study participation, and 4 months after completion of administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  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.

             -- Note: Subjects with Grade 2 hypothyroidism are an exception to this criterion and
             may qualify for the study.

          -  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.

             -- Note: Subjects with ≤ Grade 2 neuropathy, alopecia, anemia and decreased lymphocyte
             count are an exception to this criterion and may qualify for the study.

          -  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.

          -  Known history of, or any evidence of active, non-infectious pneumonitis.

          -  Active infection requiring systemic therapy.

          -  A history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Subject who received a live vaccine within 30 days of planned start of study therapy.

             -- Note: Seasonal influenza vaccines for injection are generally inactivated flu
             vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are
             live attenuated vaccines, and are not allowed.

          -  Implanted pacemaker, defibrillator, deep brain stimulator, or documented clinically
             significant arrhythmias.

          -  Evidence of increased intracranial pressure meets any of the follow criteria of raised
             intracranial pressure:

               -  midline shift >5mm

               -  clinically significant papilledema

               -  nausea/vomiting related to raised intracranial pressure

               -  reduced level of consciousness related to raised intracranial pressure

          -  Subjects who received major surgery have not recovered adequately from the toxicity
             and/or complications from the intervention prior to starting therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicity
Time Frame:21 Days
Safety Issue:
Description:Exacerbation dermatological side effects, with the rate of grade 1 & 2 dermatitis escalates to above 20% and grade 3 & 4 dermatitis rises to above 2%.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame: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
Safety Issue:
Description:
Measure:12-month Overall Survival Rate
Time Frame:1 Year
Safety Issue:
Description:Kaplan-Meir estimates
Measure:6-month progression-free survival (PFS) rate
Time Frame:6 months
Safety Issue:
Description:Kaplan-Meir estimates
Measure:Quality of Life Assessment
Time Frame:Baseline, 63 Days, 129 Days, 189 Days
Safety Issue:
Description:European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) has been used extensively in many cancer clinical trials and it is supplemented by the EORTC QLQ Brain Neoplasm 20 (BN20), which was developed specifically for patients with brain cancer. The EORTC QLQ-C30 consists of 30 items and the measurement ranges from 0 to 100, with higher score meaning better outcome in the Global Health Status domain but worse outcomes in the Functional and Symptom Scales. The EORTC QLQ-BN20 consists of 20 items and the measurement ranges from 0 to 100, with higher score meaning worse outcome in 4 scales (future uncertainty, visual disorder, motor dysfunction and communication deficit) and 7 individual items (headache, seizure, drowsiness, hair loss, itchy skin, weakness of legs and bladder control).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Eric Wong, MD

Trial Keywords

  • Melanoma Brain Metastasis
  • Metastatic Melanoma

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