Clinical trial NCT04474353: Study of Tumor Treating Fields With Hypofractionated Chemoradiotherapy in Newly Diagnosed Glioblastoma
Official title: A Phase 1 Study of Tumor Treating Fields With 5 Day Hypofractionated Stereotactic Radiosurgery and Concurrent and Maintenance Temozolomide in Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Glioblastoma
Newly Diagnosed Glioblastoma
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: NovoCure Ltd.
First posted: 2020-07-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of the combination therapy of TTFields + SRS+ Temozolomide (TMZ) for newly diagnosed glioblastoma (GBM).

Detailed description: Primary Objective:

Determine the safety of Tumor Treating Fields (TTFields) started concurrently with 5 fraction stereotactic radiosurgery (SRS) and temozolomide for newly diagnosed glioblastoma. secondary objective: Efficacy for the combination of TTFields started concurrently with 5

Eligibility criteria: Inclusion Criteria:

* Histopathologically proven newly diagnosed glioblastoma (GBM, WHO Grade IV) or molecular GBM of lower grade that will be treated as per glioblastoma (defined as IDH wild type, 1p19q not co deleted)
* Age ≥ 18 years
* A maximum tumor target diameter of less than 5 cm on the post operative MRI used for SRS planning (a 5 mm margin is added in the radiotherapy planning process, yielding a maximum diameter of the planning target volume (PTV) of less than 6 cm). If the maximum diameter is greater than 5 cm, the subject is still eligible if the PTV is less than 113 cm3 which is the volume of a 6 cm diameter sphere.
* Adequate organ function (obtained within 14 days prior to Day 0) as evidenced by:

  * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L without myeloid growth factor support for 7 days preceding the lab assessment
  * Hemoglobin (Hgb) ≥ 9 g/dL (90 g/L); \< 9 g/dL (\< 90 g/L) is acceptable if hemoglobin is corrected to ≥ 9 g/dL (90 g/L) as by growth factor or transfusion prior to Day 0
  * Platelet count ≥ 100 × 109/L without blood transfusions for 7 days preceding the lab assessment
  * Bilirubin ≤ 1.5 × upper limit of normal (ULN), except for subjects with documented history of Gilbert's disease
  * Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5 × ULN
  * Alkaline phosphatase (AP) ≤ 3 × ULN
  * Women of childbearing potential (WCBP): negative serum pregnancy test (this test is required of all women unless post menopausal, defined as 12 consecutive months since last regular menses or surgically sterile)
* Ability to tolerate MRI
* Karnofsky Performance Scale (KPS) ≥ 60
* Ability to understand and the willingness to sign (personally or by a legal authorized representative) the written IRB approved informed consent document.

Exclusion Criteria:

* Previous chemotherapy or radiotherapy for glioma
* Concurrent use of experimental therapies
* Known allergy to adhesive tapes or other skin adhesives used in medical care
* Known underlying skin hypersensitivity or other condition of the scalp with potential toxicity per pre treatment dermatology evaluation
* Subjects with the following co morbid disease or incurrent illness:

  * Subjects with known cirrhosis diagnosed with Child Pugh Class A or higher liver disease.
  * Prior malignancy except for non melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to first dose of investigational drug
  * Severe/uncontrolled inter current illness within the previous 28 days prior to first day of treatment
  * Subjects who have implantable devices that are contra indicated for use with TTFields
  * Any other significant co morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
* Subjects receiving the following medications at the time of combined TTFields and SRS:

  * Pharmacotherapy for tuberculosis or HIV as these medications are known to interact with temozolomide
  * Other chemotherapy, other investigational agents, or biologic agents for the treatment of cancer including antibodies (eg, bevacizumab, trastuzumab, pertuzumab), small molecules, or any investigational agent(s).
* Pregnant or nursing females will be excluded from the study
* History of inability to tolerate MRI

Primary outcomes:
measure: Dose-limiting Toxicity (DLTs)
timeFrame: 5 months
Secondary outcomes:
measure: Acute dose limiting toxicity
timeFrame: 1 month
measure: Progression-free Survival (PFS) at 6 Months
timeFrame: 6 months
measure: Overall Survival (OS)
timeFrame: 30 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford Universiy
name: Scott G Soltys
role: PRINCIPAL_INVESTIGATOR
References: