Optune® Plus Bevacizumab in Bevacizumab-Refractory Recurrent Glioblastoma

NCT02743078 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 2 other identifiers: RTOG 3503RF 3503
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 11

Brief Summary

This phase II trial will investigate the efficacy and safety of the addition of Optune (Tumor Treating Fields \[TTFields\] Therapy) to bevacizumab for patients with bevacizumab-refractory recurrent glioblastoma.

Conditions

Glioblastoma; Glioma; Gliosarcoma

Keywords

Glioblastoma; Glioma; Gliosarcoma; Optune; TTFields

Outcome Measures

Primary Outcomes (1)

• Overall Survival at 6 Months

  Number of participants alive at 6 months. Out of the planned 80 eligible patients, if 36 or more were alive at six months then the null hypothesis that the six-month survival rate is 35% or less would be rejected, concluding that the six-month survival is at least 35%. No testing was done due to the small number of participants resulting from early study closure.

  From registration to six months

Secondary Outcomes (4)

• Overall Survival (OS)

  From registration to study termination. Maximum follow-up was 21.8 months.

• Progression-Free Survival

  From registration to study termination. Maximum follow-up was 21.8 months.

• Number of Participants With Partial or Complete Response

  From registration to study termination. Maximum follow-up was 21.8 months.

• Number of Participants With Grade 3+ Treatment-related Adverse Events

  From registration to study termination. Maximum follow-up was 21.8 months.

Study Arms (1)

Bevacizumab and TTFields Therapy

EXPERIMENTAL

Bevacizumab starts on the first day (+/- 1 day) of Tumor Treating Fields (TTFields) therapy. Treatment is given until disease progression or the development of adverse events that require complete discontinuation.

Drug: Bevacizumab; Device: TTFields Therapy

Interventions

Bevacizumab DRUG

10 mg/kg every 2 weeks intravenously over 30 minutes.

Also known as: Avastin

Bevacizumab and TTFields Therapy

TTFields Therapy DEVICE

Device is worn continuously at least 18 hours a day on average, with 1-3 days off every four weeks.

Also known as: Optune, Tumor Treating Fields Therapy, TTF Therapy

Bevacizumab and TTFields Therapy

Eligibility Criteria

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

You may qualify if:

• Histologically proven diagnosis of glioblastoma or other grade IV malignant glioma (including variants of glioblastoma i.e., gliosarcoma, giant cell glioblastoma, etc.).
• Confirmation of tumor recurrence or progression on contrast magnetic resonance imaging (MRI) (with and without gadolinium contrast) as determined by Response assessment in neuro-oncology (RANO) criteria within 14 days prior to registration for patients who did not have recent resection of their glioblastoma or only had a stereotactic biopsy.
• Patients having undergone recent resection (within 5 weeks prior to registration) of their glioblastoma to treat current recurrence prior to study treatment must have recovered from the effects of surgery (including patient's skin having fully recovered from the surgical wound) Note: a 4-week window is required after surgery prior to starting treatment. For central nervous system (CNS) -related stereotactic biopsies, a minimum of 7 days must have elapsed prior to registration.
• Residual disease of recurrent glioblastoma is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a post-operative MRI scan must be performed prior to registration and is recommended to be within 96 hours post-surgery (although 24-48 hours would be optimum). Note: Patients who did have surgery with a post-operative contrast-enhanced scan falling outside the 5-week window prior to registration, must have a repeat MRI scan within 14 days prior to registration.
• Patients with up to two recurrences are allowed.
• Failure on bevacizumab (either as a monotherapy or a combination) as most recent regimen confirmed by tumor recurrence on MRI.
• The patient must have failed no more than one regimen of bevacizumab.
• The patient must not have received bevacizumab as an upfront treatment in newly diagnosed glioblastoma.
• There must be a minimum of 14 days (i.e., an interval equal to or greater than 14 days) since last treatment with bevacizumab and registration
• History/physical examination within 14 days prior to registration
• Karnofsky performance status ≥ 70 within 14 days prior to registration
• Age ≥ 22
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
• Platelets ≥ 75,000 cells/mm3
• Hemoglobin (Hgb) ≥ 9.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable.)

You may not qualify if:

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• Infra-tentorial tumor.
• \> 1 cm diameter of blood seen on contrast MRI (with and without gadolinium contrast)
• Major surgery such as intra-thoracic, intra-abdominal or intra-pelvic (with the exception of craniotomy), open biopsy or significant traumatic injury ≤ 4 weeks prior to registration, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to registration, or who have not recovered from side effects of such procedure or injury.
• Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain.
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration.
• Transmural myocardial infarction within the last 6 months prior to registration
• Cerebrovascular accident (CVA), transient ischemic attack (TIA) within the last 6 months prior to registration
• Pulmonary embolism (PE) within the last 6 months prior to registration
• Uncontrolled hypertension (defined by a systolic blood pressure (SBP) ≥ 160 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg while on anti-hypertensive medications) within 14 days prior to registration.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic lung disease or Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
• Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease.
• Known HIV positive patients.
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.

Sponsors & Collaborators

• RTOG Foundation, Inc.: lead
• NovoCure Ltd.: collaborator

Study Sites (11)

University of California, San Diego

La Jolla, California, 92093, United States

Location

University of California Irvine, Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Miami Cancer Institute at Baptist Health

Miami, Florida, 33176, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63100, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma; Gliosarcoma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; 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

This study stopped accrual early due to unmet targeted accrual goals with 3 subjects accrued out of 85 planned.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: RTOG Foundation

wseiferheld@acr.org

215-574-3208

Study Officials

• Manmeet Ahluwalia, MD, FACP

  RTOG Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: 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: April 5, 2016
• First Posted: April 19, 2016
• Study Start: May 9, 2017
• Primary Completion: October 15, 2019
• Study Completion: October 15, 2019
• Last Updated: June 2, 2021
• Results First Posted: November 17, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)