This phase I/II trial compares the side effects of two different treatment schedules of chemo-radiation therapy (chemotherapy plus radiation therapy) and to see how well they work in treating patients with newly diagnosed glioblastoma. Standard of care treatment after surgery consists of chemotherapy and radiation therapy to treat any remaining suspicious tumor seen on a scan. 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. Radiation therapy uses high energy x-rays used to kill tumor cells and shrink tumors. This trial compares a newer 1-week and 3-week radiation treatment schedules with temozolomide chemotherapy given at the same time for both schedules. The two treatments may provide similar tumor control but might differ slightly in the amount of side effects including a difference in the effects on lymphocyte (white blood cell involved in immune responses to fight tumors) counts.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04019262.
PRIMARY OBJECTIVES:
I. To determine whether overall survival is better with temozolomide plus 25 Gy in 5 fractions when compared to temozolomide plus 40 Gy in 15 fractions.
II. With respect to toxicity, we are specifically interested to find out which of the two arm treatments results in decreasing lymphocytopenia, a known complication of chemoradiotherapy for glioblastoma.
III. To determine whether progression free survival is better with temozolomide plus 25 Gy in 5 fractions when compared to temozolomide plus 40 Gy in 15 fractions.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I:
CHEMO-RADIATION PHASE: Patients undergo high-dose 3-dimensional (3D) conformal radiation therapy or intensity-modulated radiation therapy (IMRT) over 15-30 minutes once daily (QD) for 5 days over 1 week for a total of 5 fractions. Patients also receive high-dose temozolomide orally (PO) QD starting on the first day of radiation therapy for 5 days in the absence of disease progression or unacceptable toxicity.
ADJUVANT PHASE: Beginning 4 weeks after chemo-radiation phase, patients receive high-dose temozolomide PO QD on days 1-5. Cycles repeat monthly for up to 1 year in the absence of disease progression or unacceptable toxicity.
ARM II:
CHEMO-RADIATION PHASE: Patients undergo 3D conformal radiation therapy or IMRT over 15-30 minutes QD for 5 days per week over 3 weeks for a total of 15 fractions. Patients also receive temozolomide PO QD starting on the first day of radiation therapy for 19 days in the absence of disease progression or unacceptable toxicity.
ADJUVANT PHASE: Beginning 4 weeks after chemo-radiation phase, patients receive temozolomide PO QD on days 1-5. Cycles repeat monthly for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month and then every 1-3 months thereafter.
Lead OrganizationUniversity of Pittsburgh Cancer Institute (UPCI)
Principal InvestigatorJohn C. Flickinger
