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

NCT03430791 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: 2017-ODI-002
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Glioblastoma

Keywords

recurrent glioblastoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate According to Modified iRANO Criteria

  Objective response rate is the proportion of patients whose best overall response per modified immunotherapy response assessment in neuro-oncology (iRANO) criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy

  2 years

Secondary Outcomes (7)

• Objective Response Rate (ORR) by Standard RANO Criteria

  2 years

• Progression Free Survival (PFS)

  2 years

• Number of Toxicities

  Up to 2 years

• Rate of Treatment Compliance

  Monthly for up to 2 years

• Discontinuation Rate of Any Component of Therapy

  Up to 2 years

Study Arms (2)

Nivolumab Monotherapy

EXPERIMENTAL

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

Drug: Nivolumab 240 mg IV; Device: NovoTTF200A (Optune)

Nivolumab+Ipilimumab

EXPERIMENTAL

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

Drug: Nivolumab 240 mg IV; Drug: Nivolumab 3 mg/kg; Drug: Ipilimumab 1 mg/kg; Device: NovoTTF200A (Optune)

Interventions

Nivolumab 240 mg IV DRUG

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

Also known as: Nivolumab Monotherapy

Nivolumab Monotherapy; Nivolumab+Ipilimumab

Nivolumab 3 mg/kg DRUG

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

Also known as: Nivolumab+Ipilimumab

Nivolumab+Ipilimumab

Ipilimumab 1 mg/kg DRUG

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

Also known as: Nivolumab+Ipilimumab

Nivolumab+Ipilimumab

NovoTTF200A (Optune) DEVICE

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.

Nivolumab Monotherapy; Nivolumab+Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Baptist Health South Florida: lead
• Bristol-Myers Squibb: collaborator
• NovoCure Ltd.: collaborator

Study Sites (1)

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Related Links

• Miami Cancer Institute website

MeSH Terms

Conditions

Glioblastoma

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Did not accrue the target number of participants needed to achieve target power and statistically reliable results.

Results Point of Contact

• Title: Yazmin Odia
• Organization: Miami Cancer Institute at Baptist Health, Inc.

YazminO@baptisthealth.net

786-596-2000

Study Officials

• Yazmin Odia

  Miami Cancer Institute at Baptist Health, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, phase II trial with two parallel arms, two-stage design and appropriate stopping rules for poor efficacy. Arm A will enroll participants without prior PD1/PDL1 checkpoint inhibitor, while Arm B will enroll participants with prior PD1/PDL1 checkpoint inhibitor. The investigator expect to enroll at least 30 (15 in each Arm) and a maximum of 60 (30 in each Arm) evaluable subjects. All subjects will receive tumor treating field (TTF) therapy plus nivolumab infusions for a maximum of 24 months, plus/minus concurrent ipilimumab for a maximum of 4 doses.

Study Record Dates

• First Submitted: January 31, 2018
• First Posted: February 13, 2018
• Study Start: December 5, 2018
• Primary Completion: May 29, 2020
• Study Completion: January 27, 2021
• Last Updated: February 2, 2023
• Results First Posted: February 2, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)