Trial of Combination Tumor Treating Fields (TTF; Optune), Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma

Study Purpose

Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Histologically confirmed World Health Organization Grade IV glioblastoma with supratentorial distribution.
  • - Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria, or documented recurrent glioblastoma on biopsy.
  • - Measurable disease based on RANO criteria.
  • - Prior therapies including radiation and temozolomide.
  • - Any number of recurrences are allowed.
Resection of recurrent glioblastoma is not considered a prior treatment.
  • - From the projected start date of study treatment, the following periods must have elapsed: 4 weeks from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), or 4 weeks from any other antibodies or any other antineoplastic therapies.
  • - Must be at least 12 weeks from radiotherapy or progression outside of the high-dose radiation target volume or unequivocal evidence of progressive tumor on biopsy.
  • - All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia.
  • - Karnofsky Performance Status (KPS) ≥ 60.
  • - Adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation: - absolute neutrophil count ≥ 1,000/mcL.
  • - platelets ≥100,000/mcL.
  • - hemoglobin > 8.0 mg/dL.
  • - total bilirubin ≤ 2.0 x upper limit of normal.
  • - AST (SGOT)/ALT (SGPT) ≤ 2.5 × upper limit of normal.
  • - creatinine or creatinine clearance ≥ 60 mL/min/1.73 m2 for creatinine >ULN.
  • - Corticosteroid dose must be stable or decreasing for at least 5 days prior to enrollment.
  • - Nivolumab and ipilimumab are potentially teratogenic or abortifacient.
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to entry and for the duration of study. 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. Male subjects should agree to use adequate method of contraception starting with the first dose through 7 months after the last dose of therapy.
  • - Brain CT or MRI within 14 days prior to start of study drug.
  • - Archival tissue for evaluation of correlative objectives (if available).
  • - Ability to understand and the willingness to provide written informed consent.

Exclusion Criteria:

  • - Infratentorial disease.
  • - Bevacizumab within 2 months of enrollment.
Prior use of ipilimumab or other CTLA-4 inhibitor or prior TTFields.
  • - Tumors with known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing.
IDH1/2-mutant gliomas have a prolonged overall survival rate compared to IDH1/2-wildtype gliomas, indicating distinct natural history.
  • - History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or ipilimumab or their excipients.
  • - Current or planned participation in a study of an investigational agent or using an investigational device.
  • - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • - Active or life-threatening infection requiring intravenous or >2 weeks of systemic therapy.
  • - Prior stereotactic radiotherapy, convection enhanced delivery (CED) or brachytherapy requires a biopsy to confirm radiographic progression is consistent with progressive tumor and not treatment-related necrosis unless the recurrent lesion is outside of any prior high-dose radiation target volume or distant from the prior CED or brachytherapy site.
  • - There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, so breastfeeding must be discontinued by enrollment on study.
  • - Uncontrolled HIV or AIDS is not allowed.
Patients with known history of HIV but with undetectable viral load on antiretroviral therapy are allowed.
  • - Congestive heart failure, myocardial infarction, or hemorrhagic/ischemic stroke in the last 3 months.
  • - Active illicit drug use or diagnosis of alcoholism.
  • - Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer or other in situ malignancy that has undergone potentially curative therapy and/or with >90% probability of survival beyond 5 years.
  • - Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of start of treatment.
Incomplete recovery from any side effects of previous procedures is also exclusionary.
  • - Any significant autoimmune disorders expected to impact multiple or internal organs, excluding mild eczema or autoimmune thyroiditis treated with thyroidectomy and requiring systemic immunosuppressive or immunomodulatory therapy.
  • - Any implanted programmable cranial device, including reprogrammable ventriculoperitoneal shunt (VPS) or cochlear implants, that precludes use of TTFields (Optune) therapy.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03430791
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Baptist Health South Florida
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Yazmin Odia
Principal Investigator Affiliation Miami Cancer Institute at Baptist Health, Inc.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Terminated
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Recurrent Glioblastoma
Study Website: View Trial Website
Additional Details

Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab. The NovoTTF200A (OptuneTM) device is worn continuously for a goal of 75% or more of the time, ranging from at least 18 hours daily uninterrupted or 22 hours daily with 2-3 days off monthly. Therapy is planned for approximately 24 months. Infusions with nivolumab will start within 1 week of study start. Ipilimumab will either start with the second nivolumab infusion or at after tumor progression. Nivolumab is infused intravenously at 240 mg once every 2 weeks with or without ipilimumab for a maximum of 24 months. Ipilimumab is dosed at 1 mg/kg once every 6 weeks for a maximum of 4 doses (24 weeks). Infusions will continue until maximum doses are completed or there is confirmed tumor progression, intolerable adverse effects or withdrawal of consent.

Arms & Interventions

Arms

Experimental: Nivolumab Monotherapy

Nivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months

Experimental: Nivolumab+Ipilimumab

Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months

Interventions

Drug: - Nivolumab 240 mg IV

Nivolumab IV 240mg IV every 2 weeks for maximum of 24 months.

Drug: - Nivolumab 3 mg/kg

Nivolumab IV 3mg/kg every 2 weeks for maximum of 24 months.

Drug: - Ipilimumab 1 mg/kg

Ipilimumab IV 1 mg/kg every 6 weeks for maximum of 4 doses.

Device: - NovoTTF200A (Optune)

A device to be worn continuously for a goal of 75% of the time, ranging from 18 hours daily nonstop or 22 hours daily with 2-3 days off monthly.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Miami, Florida

Status

Address

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176

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