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| RTOG 0227 |
| Number: |
RTOG 0227 |
| Title: |
Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post-Irradiation Temozolomide For Primary Central Nervous System Lymphoma |
| Eligibility: |
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; No active infectious process; Patients who are seropositive for HIV, AIDS, or who are post organ transplant are not eligible. Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus. No active hepatitis B. Patients must sign a study-specific informed consent prior to study
|
Pre-RT
ChemoRT
Post-RTChemo |
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 daysRadiation 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
|
| Study size: |
52-64 |
| RTOG 0614 |
|---|
| Number: | RTOG 0614 |
| Title: |
A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy |
| Eligibility: |
Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis). Brain metastases must be visible on contrast-enhanced MRI or a contrast enhanced CT for patients unable to have an MRI performed <28 days prior to study entry (an allowed exception, regarding ability to image brain metastases, would be patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a baseline MRI). Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided the contrast-enhanced CT scans are obtained and are of sufficient quality. Patients must have stable systemic disease (i.e. no evidence of systemic disease progression >3 months prior to study entry). Patients who have brain metastases at initial presentation are eligible and do not need to demonstrate 3 months of stable scans. Karnofsky Performance Status of >70 within 28 days prior to study entry. Age > 18. Serum creatinine and total bilirubin obtained <28 days prior to study entry; with adequate kidney and liver function as defined in the protocol. BUN < 20 mg/dL <28 days prior to study entry; MMSE score >18 within 28 days prior to study entry. Patient must provide study specific informed consent prior to study entry. Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection. Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry. Patients receiving systemic therapy are eligible for this study if given >14 days prior to study entry and given no sooner than >14 days post RT completion. Negative serum pregnancy test (in women of childbearing potential) <7 days prior to study entry. Women of childbearing potential and men who are sexually active must practice adequate contraception. Complete history and general physical examination < 28 days prior to study entry. No prior allergic reaction to memantine. No current alcohol or drug abuse. No chronic short-acting benzodiazepine use. No intractable seizures while on adequate anticonvulsant therapy.
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| Treatment |
Arm 1
WBRT 37.5Gy/15 fractions + memantine *
Arm 2
WBRT 37.5Gy/15 fractions + placebo*
*Memantine/placebo to be administered during and after WBRT for a total of 24 weeks.
|
| Study size: | 536 |
| RTOG 0627 |
|---|
| Number: | RTOG 0627 |
| Title: |
Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme |
| Eligibility: |
Histologically proven diagnosis of GBM. Since gliosarcoma is a variant of GBM, gliosarcoma is also an eligible diagnosis. 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. Patients accrued to stage 1 or stage 1B must have tumors overexpressing at least 2 known dasatinib targets (SRC, KIT, PDGFR, and EPHA2). Patients accrued to stage 2 do not require overexpression of 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. 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. There must be unequivocal radiographic evidence for tumor progression by MRI or CT scan, and the same type of scan (i.e., MRI or CT) must be used throughout the period of protocol treatment for tumor measurement. Patients must be on a stable or decreasing dose of corticosteroids for at least 5 days before the baseline MRI/CT is performed. Patients having undergone recent surgery for recurrent/progressive disease are eligible as long as they have recovered from the effects of surgery. The primary endpoint is progression-free survival after 6 months of treatment; therefore, patients who recently underwent resection without measurable disease post-operatively are also eligible although radiographic response rate will be calculated for patients with measurable disease at study entry. Measurable disease is not required for eligibility in patients who recently underwent resection as long as the following conditions are met as applicable: Progression of disease led to the surgery; Gliadel wafers were not placed during the most recent surgery; Neither convection enhanced delivery nor catheters for infusion of chemotherapy were used during the most recent surgery; Radioactive seeds were not placed during the most recent surgery; The histology of the most recent surgery documented recurrent/persistent/progressive malignant glioma. Women of childbearing potential must have a negative B HCG pregnancy test 3 days prior to registration. Patient must sign study-specific informed consent prior to study entry.
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|
|
| Treatment: |
Dasatinib |
| Study size: | 84 (Stage 1: 29; Stage 1B; 29 (maximum); Stage 2: 26 (maximum) |
| RTOG 0825 |
|---|
| Number: | RTOG 0825 |
| Title: |
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 |
| Eligibility: |
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. History/physical examination within 14 days prior to registration. 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. Age > 18. CBC/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) > 1,800 cells/mm3; Platelets > 100,000 cells/mm3; Hemoglobin > 10.0 g/dl. Adequate renal function, defined as follows: BUN < 30 mg/dl within 14 days prior to study registration; Creatinine < 1.7 mg/dl within 14 days prior to study registration; Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg. Adequate hepatic function, defined as follows: Bilirubin < 2.0 mg/dl within 14 days prior to study registration; ALT/AST < 3 x normal range within 14 days prior to study registration. Systolic blood pressure < 160 mg Hg or diastolic pressure < 90 mg Hg within 14 days prior to study registration. Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior study registration. Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study registration. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices); In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin. Patient must provide study specific informed consent prior to study entry. Women of childbearing potential and male participants must practice adequate contraception. For females of child-bearing potential, negative serum pregnancy test within 14 days prior to registration.
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|
|
Concurrent Radiation/ Temozolomide
Adjuvant Temozolomide +
Bevacizumab/Placebo |
Radiation (30 Gy in 2 Gy fractions)
Concurrent daily temozolomide (qd X 21 d)
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
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| Study size: | 720 |
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