A Phase II Study of Optune (NovoTTF) in Combination With Bevacizumab (BEV) and Temozolomide (TMZ) in Patients With Newly Diagnosed Unresectable Glioblastoma (GBM)

NCT02343549 | Terminated Phase 2 Results DMC

• 2 other identifiers: LCI-NEU-NOV-00100010270
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

All patients will complete best standard of care radiation, temozolomide and bevacizumab (6 weeks). Within two weeks of completion of this initial treatment period, study patients will be fitted with the NovoTTF-100A System and treated continuously. They will be treated with TTFields for 12 months for an average of 18 hours per day. The patient may elect to take a treatment break for a total of 3 days per month, for each month and still be in compliance. This will consist of wearing four electrically insulated electrode arrays on the head. The patients will also continue with maintenance temozolomide/ bevacizumab.

Conditions

Cancer of Brain and Nervous System

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 12-Month Survival

  Twelve-month survival was determined for each subject as a binary variable indicating whether or not the subject was alive at 12 months from initiation of chemoradiation. Determination of this endpoint occurs after the subject has at least 12 months of follow-up, unless they have died sooner.

  Evaluated over 12 months

Secondary Outcomes (6)

• Overall Survival (OS)

  From date of treatment start to date of death, or censored as described above; assessed for approximately 5 years

• Progression Free Survival (PFS)

  From date of treatment start to date of progression/death, or censored as described above; assessed for approximately 2 years.

• Number of Participants With Objective Response

  From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for an average of 7 months)

• Number of Participants With Disease Control

  From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for an average of 7 months).

• Duration of Response

  From date of first response to date of progression/death, or censored as described above; assessed for approximately 2 years.

Study Arms (1)

Planned RT + TMZ + BEV + NovoTTF100A Device

EXPERIMENTAL

Best standard of care radiation therapy (RT, 2 Gy given daily 5 days per week), temozolomide (TMZ, 75 mg/m2 administered daily), and bevacizumab (BEV, 10 mg/kg administered every 2 weeks as an IV infusion) for 6 weeks. After completion of chemoradiation, NovoTTF100A system was initiated, to be worn on average 18 hours or more a day for up to 12 months. The patients also continued with maintenance TMZ/BEV.

Device: NovoTTF100A; Drug: Bevacizumab; Drug: Temozolomide

Interventions

NovoTTF100A DEVICE

Also known as: Optune(TM)

Planned RT + TMZ + BEV + NovoTTF100A Device

Bevacizumab DRUG

Also known as: Avastin

Planned RT + TMZ + BEV + NovoTTF100A Device

Temozolomide DRUG

Also known as: Temodar

Planned RT + TMZ + BEV + NovoTTF100A Device

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 22 years of age
• Have undergone a brain biopsy via stereotactic or open technique
• Pathological evidence of GBM using WHO classification criteria
• Planned 6 weeks of concurrent chemoradiotherapy post-biopsy concomitant with temozolomide (45-70Gy)
• Karnofsky scale greater than or equal to 70
• Life expectancy at least 3 months
• Baseline hemoglobin of \> 8.0 gm/dL (with or without transfusion)
• Adequate coagulation defined as PT and INR \< 1.5 times the upper limit of normal
• Signed informed consent
• Able to start bevacizumab at least 2 weeks but no more than 4 weeks from date of biopsy
• Able to tolerate MRI of brain and have measurable disease.
• Participants of childbearing age must use effective contraception for at least 6 months following completion of treatment.

You may not qualify if:

• Enrolled in another clinical treatment trial
• Pregnant or Breast-feeding
• Any other malignancy aside from localized basal cell or squamous cell carcinoma of the skin
• Significant co-morbidities at baseline which would prevent maintenance temozolomide
• Thrombocytopenia (platelet count \< 100 x 103 )
• Neutropenia (absolute neutrophil count \< 1.5 x 103 )
• CTC grade 4 non-hematological toxicity (except for alopecia, nausea, vomiting)
• Significant liver function impairment - AST or ALT \> 3 times the upper limit of normal
• Total bilirubin\> 2 times the upper limit of normal
• Significant renal impairment (serum creatinine\> 1.7 mg/dL)
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• Infra-tentorial tumor
• Evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea, or reduced level of consciousness)
• History of hypersensitivity reaction to temozolomide or a history of hypersensitivity to DTIC or hydrogel
• Inability to adequately cover treatment area with TTFields (Tumor Treating Fields)

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• NovoCure Ltd.: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Neurologic Manifestations

Interventions

Bevacizumab; Temozolomide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Levine Cancer Institute

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Ashley Sumrall, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: January 22, 2015
• Study Start: January 1, 2015
• Primary Completion: July 11, 2020
• Study Completion: July 11, 2020
• Last Updated: November 3, 2022
• Results First Posted: August 10, 2021

Record last verified: 2021-09

Locations

US (1)