Tumor Treating Fields With Chemoradiation in Newly Diagnosed GBM

• ClinicalTrials.gov Identifier: NCT03705351
• Recruitment Status: Active, not recruiting
• First Posted: October 15, 2018
• Last Update Posted: April 13, 2021
• Sponsor: Providence Health & Services
• Collaborators: University of California, San Francisco; NovoCure Ltd.
• Information provided by (Responsible Party): Providence Health & Services

Study Description

Brief Summary:

The study is an open-label pilot study in newly diagnosed glioblastoma patients following surgery. Eligible patients will receive treatment with tumor treating fields therapy using the Optune device starting less than 2 weeks prior to start of chemoradiation. Patients will receive radiation and temozolomide at a routine treatment dose and schedule.

Condition or disease	Intervention/treatment	Phase
Glioblastoma; Cancer of Brain; Glioblastoma Multiforme; Brain Tumor	Device: Tumor Treating Fields; Drug: Temozolomide; Radiation: Radiation Therapy	Phase 1

Detailed Description:

The study is an open-label pilot study in newly diagnosed glioblastoma patients following surgery. Eligible patients will receive treatment with tumor treating fields therapy using the Optune device starting less than 2 weeks prior to start of chemoradiation. Patients will receive radiation and temozolomide at a routine treatment dose and schedule.

The expected toxicity is skin related, and patients will be followed closely with weekly skin and neurological examinations during radiation therapy and for 8 weeks afterwards to capture any delayed toxicity as they begin adjuvant therapy per routine treatment. As long as study treatment is tolerated and their conditions remain stable, patients will continue the treatment for up to 24 months.

Prior to enrollment, an exploratory analysis of radiation dosimetry will be performed by phantom modeling incorporating the Optune arrays. The study incorporates three stages of recruitment to confirm the safety of combining tumor treating fields therapy with concurrent chemoradiation: a safety lead-in cohort of the first 6 patients enrolled, a second safety lead-in cohort of 9 patients, and an expansion cohort with 15 additional patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: The study is an open-label pilot study. Following surgery, eligible patients will start tumor treating fields therapy with the Optune device less than 2 weeks prior to radiation and temozolomide given at a dose and schedule conforming to routine treatment.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Tolerability of Tumor Treating Fields (TTFields) Combined With Chemoradiation in Newly Diagnosed Glioblastoma (Unity)
• Actual Study Start Date: December 2, 2019
• Estimated Primary Completion Date: November 1, 2023
• Estimated Study Completion Date: November 1, 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment; Patients will receive trimodal therapy consisting of tumor treating fields therapy with the Optune device concurrent with temozolomide and radiation therapy.

Device: Tumor Treating Fields; Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM). Treatment will begin approximately 1 week prior to start of radiation and temozolomide treatment and continue concurrently throughout the duration of the study.; Other Names: Optune; Novocure; Drug: Temozolomide; Patients will be given temozolomide according to routine treatment dosing and schedule.; Other Name: Temodar; Radiation: Radiation Therapy; Patients will be given radiation therapy according to routine treatment dosing and schedule.

Outcome Measures

Primary Outcome Measures :

1. Rate of treatment-related adverse events associated with trimodal therapy [ Time Frame: 15 weeks (8 weeks after completion of trimodal therapy) ]
   Number of patients who experienced a treatment-related adverse event
2. Severity of treatment-related adverse events associated with trimodal therapy [ Time Frame: 15 weeks (8 weeks after completion of trimodal therapy) ]
   Number of patients who experienced a treatment-related serious adverse event based on the NCI Common Terminology Criteria for Adverse Events (version 4.03)

Secondary Outcome Measures :

1. Progression-free survival at 6 months and 24 months [ Time Frame: 24 months ]
   Number of patients who are progression free at 6 months and 24 months
2. Overall Survival Rate [ Time Frame: 24 months ]
   Number of patients alive at 24 months

Eligibility Criteria

• Ages Eligible for Study: 22 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. GBM or Gliosarcoma by histology
2. MGMT methylation status and IDH mutation status must be assessed at the study site or patient's referral center. MGMT status will be used for stratification purposes but will not exclude patients from this study if they are either methylated, unmethylated, or indeterminate, or in process at the time of enrollment. Similarly, subjects with tumors that are IDH mutated or wild type are both eligible.
3. Supratentorial location
4. Maximum safe resection (including patients who can only safely be biopsied)
5. 22 years of age or older
6. Estimated survival of at least 12 weeks
7. KPS 70% or greater at time of entry to study
8. Patient provided written informed consent, or provided by a legally authorized representative
9. Willingness to comply with all procedures, including visits or evaluations, imaging, laboratory tests and rescue measures
10. Acceptable method of birth control (see appendix)
11. Have had a contrast-enhanced brain MRI after tumor resection procedure. If biopsy alone performed, cranial CT may be used in place of MRI, only if the patient had a preoperative MRI scan within 14 days of the biopsy.
12. The following time period must have elapsed prior to study enrollment: 3-6 weeks (21-42 days) from time of definitive surgery or 2-4 weeks (14-28 days) from the time of biopsy, for those who were only able to safely have a biopsy and not full resection.

Exclusion Criteria:

1. Craniotomy or stereotactic biopsy wound dehiscence or infection
2. Known by history to be HIV positive or to have an AIDS-related illness, active Hepatitis B, or active Hepatitis C (testing not required)
3. Presence of skull defects (bullets, metal fragments, missing bone)
4. Patients with implanted electronic medical devices (including but not limited to: pacemaker, vagal nerve stimulator, or pain stimulator)
5. Prior invasive malignancy, unless disease free for 3 or more years, with the exception of basal cell carcinoma, cervical carcinoma in situ, or melanoma in situ
6. Recurrent malignant gliomas or higher grade gliomas transformed from previous low grade (II) glioma
7. Patients with any current Primary brain stem or spinal cord tumor
8. Prior use of temozolomide
9. Prior treatment with Avastin
10. Individuals requiring >8mg of dexamethasone per day within 7 days prior to Day 1 (high dose steroid taper following craniotomy with >8mg of dexamethasone is allowed during the screening period, but subjects must taper down to 8mg or less of dexamethasone (or bioequivalent) within 7 days prior to Day 1).

11. Clinically significant lab abnormalities at screening showing bone marrow, hepatic, and renal dysfunction:

    • Thrombocytopenia (platelet count < 100 x 103/μL)
    • Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
    • Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
    • Total bilirubin > upper limit of normal
    • Significant renal impairment (serum creatinine > 1.7 mg/dL)
12. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting) at screening
13. Inability to swallow pills
14. Clinically significant or unstable comorbid medical condition, per investigator discretion (for example, active or uncontrolled infection requiring systemic therapy, including known HIV or hepatitis B or C virus)
15. Known current alcohol or drug abuse, per investigator discretion. Prior history of substance abuse is permissible if subject has been sober for the past 3 years.
16. Any clinically significant psychiatric condition that would prohibit patient willingness or ability to successfully complete study procedures, per investigator discretion
17. Patients with an allergy to or an inability to have gadolinium contrast dye administered with MRI
18. Patients with aneurysm clips or implanted metal objects in the brain
19. Patients with significant skin breakdown on the scalp
20. Patients who cannot receive standard of care radiation therapy and can only receive hypofractionated radiation due to age and poor performance status , per investigator discretion

Contacts and Locations

Locations

United States, California

University of California San Francisco

San Francisco, California, United States, 94143

United States, Oregon

Providence St. Vincent Medical Center

Portland, Oregon, United States, 97225

Sponsors and Collaborators

Providence Health & Services

University of California, San Francisco

NovoCure Ltd.

Investigators

• Principal Investigator: Ricky Chen, MD; Providence Health and Services

More Information

Additional Information:

Providence Brain & Spine Institute Clinical Research 

• Responsible Party: Providence Health & Services
• ClinicalTrials.gov Identifier: NCT03705351
• Other Study ID Numbers: UNITYGBM01
• First Posted: October 15, 2018
• Last Update Posted: April 13, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Providence Health & Services:

temozolomide; tumor treating fields; optune; novocure; glioblastoma; brain tumor

Additional relevant MeSH terms:

Glioblastoma; Brain Neoplasms; Neoplasms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents