Combination Therapy for Glioblastoma

Overseen By Michael Dominello, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Barbara Ann Karmanos Cancer Institute

Must not be taking: Bevacizumab, Carmustine, others

Disqualifiers: Recurrent glioblastoma, Metastatic GBM, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

2 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the side effects of partial brain radiation therapy, temozolomide, chloroquine, and tumor treating fields therapy for the treatment of newly diagnosed glioblastoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chloroquine is normally used to treat strains of malaria and prior preclinical and clinical data suggests that it may increase the efficacy of both radiation and tumor treating fields therapy. Tumor treating fields therapy uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and potentially causing cancer cells to die. The purpose of this study is to determine the safety of partial brain radiation therapy, temozolomide, chloroquine, and tumor treating fields therapy in patients with gliobastoma

Research Team

Michael Dominello, MD

Principal Investigator

Barbara Ann Karmanos Institute

Eligibility Criteria

This trial is for adults with newly diagnosed glioblastoma who have recovered from surgery without complications. They must not have had previous chemotherapy or radiosensitizers for head and neck cancers (except certain conditions), no severe heart disease, eye disorders, or other major illnesses that could interfere with the treatment. Women of childbearing potential must use effective contraception and have a negative pregnancy test.

Inclusion Criteria

My kidney function, measured by creatinine clearance, is adequate.

I have been diagnosed with a grade IV brain tumor.

I have signed the consent form for this study.

Exclusion Criteria

History of hypersensitivity to temozolomide or excipients

Severe, active, co-morbidity defined as follows: Moderate or severe hepatic impairment (Child-Pugh category B or higher [score of 7 or higher ]); unstable angina and/or congestive heart failure within the last 6 months; transmural myocardial infarction within the last 6 months; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days prior to enrollment; New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to enrollment; History of stroke, cerebral vascular accident (CVA), or transient ischemic attack within 6 months (except if intra- or post-operative); serious and inadequately controlled cardiac arrhythmia; acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment; uncontrolled human immunodeficiency virus (HIV) with CD4 count < 200; note, however, that HIV testing is not required for entry into this protocol; Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy; Subjects treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study, except intra-operative therapy to guide resection or experimental imaging without therapeutic intent; Inability to undergo contrast-enhanced MRI scans; Presence of implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, or other implanted electronic devices in the brain; Documented clinically significant arrhythmia or severe ischemic heart disease; Patients with underlying ocular disorders, including but not limited to: maculopathy, macular degeneration, and retinopathy

I have been cancer-free for 5 years, except for certain skin cancers and early-stage cancers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants undergo 30 fractions of 3D CRT or IMRT and receive temozolomide and chloroquine daily for the duration of radiation therapy up to day 49

7 weeks

Daily visits for radiation therapy

Adjuvant Treatment

Beginning 4 weeks after radiation, participants receive temozolomide and chloroquine with TTF therapy for up to 6 cycles, potentially extending to 12 cycles

6-12 months

Monthly visits for each cycle

Follow-up

Participants are monitored monthly for 3 months after completion of study treatment

3 months

Monthly visits

Treatment Details

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Chloroquine
• Intensity-Modulated Radiation Therapy (IMRT)
• Temozolomide
• Tumor Treating Fields Therapy (TTF)

Trial Overview The study tests the combination of partial brain radiation therapy, temozolomide (a chemotherapy drug), chloroquine (an antimalarial drug thought to enhance cancer treatments), and tumor treating fields therapy (TTF) which uses electric fields to disrupt cancer cell growth in patients with glioblastoma.

Participant Groups

Group I: Treatment (radiation therapy, temozolomide, chloroquine, TTF) Experimental Treatment 5 Interventions

Patients undergo 30 fractions of 3D CRT or Intensity-modulated radiation therapy (IMRT) and receive temozolomide by mouth (PO) and chloroquine PO daily from day 1 for the duration of radiation therapy up to day 49. Treatment continues in the absence of disease progression or unacceptable toxicity. ADJUVANT TREATMENT: Beginning 4 weeks after the last day of radiation therapy, patients receive temozolomide PO QD on days 1-5 and chloroquine PO daily on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients demonstrating continued benefit may continue to receive temozolomide and chloroquine for up to 12 cycles. Patients also undergo TTF therapy over 18 hours or longer per day.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+