Clinical trial NCT03705351: Tumor Treating Fields With Chemoradiation in Newly Diagnosed GBM
Official title: Safety and Tolerability of Tumor Treating Fields (TTFields) Combined With Chemoradiation in Newly Diagnosed Glioblastoma (Unity)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Glioblastoma
Cancer of Brain
Glioblastoma Multiforme
Brain Tumor
Keywords: temozolomide
tumor treating fields
optune
novocure
glioblastoma
brain tumor
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: NovoCure Ltd.
First posted: 2018-10-15
Enrollment: 7
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Rate of Treatment-Related Adverse Events Associated With Trimodal Therapy
timeFrame: 15 Weeks (8 weeks after completion of trimodal therapy)
measure: Severity of Treatment-Related Adverse Events Associated With Trimodal Therapy
timeFrame: 15 weeks (8 weeks after completion of trimodal therapy)
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: Day 106
measure: Progression-free Survival at 6 Months and 24 Months
timeFrame: 6 months and 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
Study officials:
affiliation: Providence Health and Services
name: Ricky Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: