Adult Clinical Trials: BRAIN

RTOG 0227

Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post-Irradiation Temozolomide For Primary Central Nervous System Lymphoma

• Primary CNS lymphoma based on positive biopsy, or CSF, or vitreous cytology (in association with measurable intraparenchymal tumor)
•  Life expectancy of > 8 weeks; Zubrod of 0-2;
• Absolute granulocyte count > 1500/mm3; platelet count > 100,000/mm3; creatinine clearance > 50; Bilirubin, SGOT (AST), alkaline phosphatase < 2 x institutional upper limits of normal.
• No evidence of systemic lymphoma.
• No prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer) unless disease free for at least 5 years.
•  No prior radiotherapy to the brain or head/neck;
• No prior chemotherapy; No history of idiopathic sensitivity to any of the study drugs

Treatment

Pre-Irradiation Chemotherapy: Rituximab: 375 mg/m2 3 days prior to first

cycle of MTX; Methotrexate (MTX) i.v. 3.5 g/m2 with leucovorin rescue on weeks 1, 3, 5, 7, 9 for a total of 5 cycles; Temozolomide (TMZ) 100 mg/m2 per day for 5 days Radiation Therapy: Whole brain radiation therapy (WBRT) 1.2 Gy b.i.d. fractions, 5 days/wk on weeks 11,12,13 for a total of 36 Gy

Post-RT Chemotherapy: Temozolomide (TMZ) 200 mg/m2 per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles

RTOG 0320: BRAIN

A Phase III Trial Comparing Whole Brain Radiation and Stereotactic Radiosurgery Alone Versus with Temozolomide or Erlotinib in Patients with Non-Small Cell Lung Cancer and 1-3 Brain Metastases

• Histologically confirmed non-small cell lung cancer with 1-3 brain metastases
• Well-circumscribed brain lesion less than or equal to 4cm in size.
• If multiple lesions are present and one is at the maximum diameter, the others must not exceed 3cm in size.

Treatment

Arm1: WBRT + SRS
Arm 2: WBRT + SRS + Temozolomide
Arm 3: WBRT + SRS + Erlotinib

RTOG 0525: BRAIN

Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma Histopathologically proven diagnosis of glioblastoma multiforme. Patients must have at least 1 block of tissue available for analysis of MGMT status; fresh frozen tumor tissue acquisition is encouraged. Diagnosis must be made by surgical biopsy or excision. The tumor must have a supratentorial component. Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration. A diagnostic contrast-enhanced MRI or CT scan (if MRI is not available) of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy, within 28 days prior to study registration. Preoperative and postoperative scans must be the same type. If CT scans were performed perioperatively, a CT and an MRI should be performed before randomization. Patients diagnosed only by stereotactic biopsy do not require the postoperative scan. However, these patients will only be eligible once review of the tissue block determines that an adequate sample is available for molecular analysis. Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained and are of sufficient quality. Therapy must begin 5 weeks after surgery.

• History/physical examination within 14 days prior to study registration.
• Karnofsky performance status of > 60.
• CBC/differential obtained within 14 days prior to study registration, with adequate bone marrow function as defined as: Absolute neutrophil count (ANC) > 1500 cells/mm3; Platelets > 100,000 cells/mm3; Hemoglobin > 10 g/dl.
• If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member.

Treatment

Radiation (60 Gy in 2 Gy fractions)
Concurrent daily TMZ
(qd x 49 d maximum)
Followed by:
Arm 1 (Standard Arm)
TMZ d 1-5 of 28-d cycle
6 cycles*
Arm 2 (Experimental Arm)
TMZ d 1-21 of 28-d cycle
6 cycles*
* Up to 12 cycles may be given if the patient demonstrates continued improvement on MR scan, decreasing corticosteroid requirement, improvement in performance status, or improvement in neurologic function.

RTOG 0627: BRAIN

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