Protocol Summary

Protocol No.: OCR14089

Sponsor Protocol No.: NRG-BN001

Study Title
Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy versus Conventional Photon Irradiation with Concomitant and adjuvant Temozolomide in Patients with Newly Diagnosed Glioblastoma.

Principal Investigator(s)
Rotondo, Ronny

Objective
This randomized phase II trial studies how well dose-escalated photon intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy works compared with standard-dose radiation therapy when given with temozolomide in patients with newly diagnosed glioblastoma.

Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as temozolomide, may make tumor cells more sensitive to radiation therapy. It is not yet known whether dose-escalated photon IMRT or proton beam radiation therapy is more effective than standard-dose radiation therapy with temozolomide in treating glioblastoma.

Description
In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Phase: Phase II

Age Group: Adult

Scope: National

Treatment
Arm A1: Control
- Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT QD, 5 days a week for 23 fractions plus a boost of 7 additional fractions.

Arm B: Photon IMRT
- Patients undergo dose-escalated and -intensified photon IMRT QD, 5 days a week for a total of 30 fractions.

Arm A2: Control
- Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT as in Arm A1.

Arm C: Proton beam radiation therapy
- Patients undergo dose-escalated and -intensified proton beam therapy QD, 5 days a week for a total of 30 fractions.

Detailed Eligibility
INCLUSION CRITERIA:
PRIOR TO STEP 1 REGISTRATION
1. A diagnostic contrast-enhanced magnetic resonance imaging (MRI) (no other scan type allowed) of the brain must be performed postoperatively within 72 hours of resection and meet protocol-defined criteria.
2. The GBM tumor must be located in the supratentorial compartment only

PRIOR TO STEP 2 REGISTRATION
1. Histologically proven diagnosis of glioblastoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration
2. Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient quantity for analysis of O6-methylguanin-DNA-methyltransferase (MGMT) status
3. Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present
4. Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy or cavitron ultrasonic suction aspirator (CUSA) technique are not allowed
5. History/physical examination within 14 days prior to step 2 registration
6. The patient must have recovered from effects of surgery, postoperative infection, and other complications within 14 days prior to step 2 registration
7. Documentation of steroid doses within 14 days prior to step 2 registration
8. Labs within protocol defined limits

EXCLUSION CRITERIA:
1. 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)
2. Recurrent or multifocal malignant gliomas
3. Any site of distant disease
4. Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable (except temozolomide)
5. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
6. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
7. Severe, active co-morbidity, as defined by the protocol
8. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
9. Patents treated on any other therapeutic clinical protocols within 30 days prior to step 2 registration
10. Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker, or severe claustrophobia)

Applicable Disease Sites

Brain and Nervous System

Therapies Involved
Radiotherapy

Drugs Involved
Temodar (Temozolomide)
Temozolomide

Participating Institutions
UF Gainesville
UF Jacksonville

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02179086