Adult Clinical Trials: BRAIN

RTOG 0627

Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme
Histologically proven diagnosis of GBM. The patient must consent to submission of tissue for central pathology review. Patients who have already undergone central pathology review through their enrollment on another RTOG GBM trial do not need to consent to having their material re-reviewed by the central pathologist for this study. All patients must consent to molecular analysis of pre-dasatinib tumor tissue. The first 27 patients must have tumors overexpressing at least 2 known dasatinib targets (SRC, KIT, PDGFR, and EPHA2).

• History and physical examination, including height and weight, within 10 days prior to registration on study.
• Brain MRI with and without gadolinium within 10 days prior to registration on study. Contrast-enhanced CT scans are allowed for patients who cannot undergo MRI scanning.
• Karnofsky performance status > 60. o Age > 18.
• CBC/differential obtained within 10 days prior to registration on study, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) > 1,000 cells/mm3; Platelets > 75,000 cells/mm3; Hemoglobin > 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.); Leukocytes > 3,000/ cells/mm3; Absolute lymphocyte count (ALC) > 500 cells/mm3.
• Adequate liver function within 10 days prior to registration on study, defined as follows: Total bilirubin < 1.5 X institutional upper limit of normal; AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal. Adequate renal function within 10 days prior to registration on study, defined as follows: Creatinine < 3 X institutional upper limit of normal OR creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• All patients must have undergone prior treatment with radiotherapy and temozolomide. No other prior treatments are allowed.
• Patients having undergone recent surgery for recurrent/progressive disease are eligible as long as they have recovered from the effects of surgery.

Treatment

            Dasatinib 100 mg BID

 

RTOG 0825

Phase III Double-Blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

• Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) confirmed by central review prior to step 2 registration. Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of MGMT status and determination of molecular profile, as specified in the protocol.
• The tumor must have a supratentorial component.
• The patient must have recovered from the effects of surgery, postoperative infection, and other complications before study registration. A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy.
•  The postoperative scan must be performed within 28 days prior to step 1 registration. An MRI or CT scan (potentially in addition to the postoperative scan) must be obtained within 1 week prior to registration and must not demonstrate significant postoperative hemorrhage defined as > 1 cm diameter of blood.
• The radiation planning MRI or CT scan may be used to determine presence of hemorrhage.
• Documentation of steroid doses within 14 days prior to registration.
• Karnofsky performance status > 70.

Treatment:

Concurrent Radiation/ Temozolomide- Radiation (30 Gy in 2 Gy fractions)
Concurrent daily temozolomide (qd X 21 d) then

Adjuvant Temozolomide +
Bevacizumab/Placebo
Arm 1
(Final 3 weeks of chemoradiation)
Radiation (30 Gy in 2 Gy fx) + daily TMZ
(qd x 21 d) + placebo q 2 wks (continues without stop)

4 weeks after completion of chemoradiation:
Temozolomide d 1-5 of 28-d cycle
+ placebo q 2 wks; 12 cycle maximum**

**Bevacizumab at progression at physician discretion

Arm 2
(Final 3 weeks of chemoradiation)
Radiation (30 Gy in 2 Gy fx) + Daily TMZ
(qd x 21 d) + bevacizumab q 2 wks (continues without stop)

4 weeks after completion of chemoradiation:
Temozolomide d 1-5 of 28-d cycle + bevacizumab q 2 wks; 12 cycle maximum**

**Bevacizumab at progression at physician discretion