|
| 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 0320 |
|---|
| Number: |
RTOG 0320 |
| Title: |
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 |
| Eligibility: |
Histologically confirmed non-small cell lung cancer with 1-3 intraparenchymal brain metastases; diagnostic contrast-enhanced MRI demonstrating presence of 1-3 brain metastases performed within two weeks prior to registration; well-circumscribed intraparenchymal brain lesion with maximum tumor diameter (<4.0 cm per lesion). If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter; Patients who have undergone subtotal resection are eligible providing residual disease is 4.0 cm in maximum diameter; no metastases to brain stem, midbrain, pons, medulla or within 10 mm of the optic apparatus (optic nerves and chiasm); no clinical or radiographic evidence of progression of extracranial disease in the month prior to randomization; age 18 years or older; Zubrod 0-1; Neurologic Function Status 0, 1, or 2; adequate bone marrow reserve (hemoglobin > 8 grams, absolute neutrophil count >1000/mm3, platelets > 100,000/mm3); all liver function tests (AST/SGOT, alkaline phosphatase, total bilirubin, LDH) < 2 x institutional upper limit of normal (uln); serum creatinine < 1.5 x uln; If the liver function tests, specifically the alkaline phosphatase is elevated above the allowed limit, but this is deemed to be due to bone metastases and not liver metastases, the patient is eligible. Patients randomized to receive erlotinib who are on enzyme inducing seizure medicines including phenytoin, carbamazepine, rifampicin, barbiturates must be converted to a non-enzyme inducing anti-seizure medication.
Patients who present with symptoms of brain metastases at the time of initial diagnosis are eligible and do not need to demonstrate one month of stable scans.
Patients who present with synchronous brain metastases at the time of the initial diagnosis of lung cancer are eligible.
|
| Treatment: |
Arm 1: WBRT + SRS
Arm 2: WBRT + SRS + temozolomide
Arm 3: WBRT + SRS + erlotinib
|
| Study size: | 381 |
| RTOG 0424 |
|---|
| Number: |
RTOG 0424 |
| Title: |
A PHASE II STUDY OF A TEMOZOLOMIDE-BASED CHEMORADIOTHERAPY REGIMEN FOR HIGH RISK LOW-GRADE GLIOMAS |
| Eligibility: |
Histological proof of a unifocal or multifocal supratentorial WHO grade II astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic), oligodendroglioma, or oligoastrocytoma confirmed by central pathology review prior to registration. Patient must have at least three of the following risk factors: age > 40 years; largest preoperative diameter of tumor > 6 cm; tumor crosses midline; tumor subtype of astrocytoma (astrocytoma dominant); preoperative Neurological Function Status (NFS)> 1. Zubrod 0-2. Mandatory evaluations: required laboratory tests within 14 days prior to registration: CBC with differential, ANC > 1500/mm3, platelet count > 100 x 109/l; Biochemistries including sodium, potassium, serum creatinine < 1.5 mg/dl; total bilirubin < 1.5 mg/dL, SGOT (AST) or SGPT, and alkaline phosphate < 2 x institutional normal range. History and physical exam (including neurologic exam) with documentation of baseline signs, symptoms and medications, including steroids and anticonvulsants within 14 days prior to registration. Pre-operative and post-operative MRIs with and without contrast obtained within 4 weeks of date of surgery. The MRI must include T1 weighted images with and without contrast and T2 weighted images. Pre-op or post-op CT scans are not acceptable. See Section 11.1 for details. Chest X-ray within 12 weeks prior to registration. Negative serum pregnancy test for women of childbearing potential within 5 days prior to registration. Signed study-specific informed consent prior to study entry. Age > 18. Tissue available for analysis of MGMT status and tissue banking.
|
| Treatment: |
Daily temozolomide plus concurrent radiotherapy (54 Gy/30 fractions/6 weeks) followed by temozolomide x 12 cycles |
| Study size: | 97 |
| RTOG 0513 |
|---|
| Number: |
RTOG 0513 |
| Title: |
A Phase I/II Trial of Temozolomide, Motexafin Gadolinium, and 60 Gy Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma Multiforme |
| Eligibility: |
Histopathologically confirmed newly diagnosed GBM within 4 weeks of registration. Diagnosis must be made by surgical biopsy or excision. The patient must have recovered from the effects of surgery or postoperative infection and other complications. The tumor must be supratentorial in location as determined by a diagnostic contrast-enhanced MRI or CT performed preoperatively: an MRI performed postoperatively within 28 days prior to registration (preferably within 72 hours of surgery), prior to the initiation of radiotherapy; a postoperative scan is not required if the patient was diagnosed by stereotactic biopsy and a pre-biopsy MRI was performed. If a pre-biopsy CT scan only was done, a post-biopsy MRI must be obtained. Zubrod performance status 0-1. Neurologic function status 0-2. Age > 18. Therapy must begin < 5 weeks after surgery. CBC/differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) > 1800 cells/mm3; Platelets > 100,000 cells/mm3; Hemoglobin > 8 g/dL: If anemia is present to the extent that the hemoglobin is < 8 g/dL, then correction by transfusion is indicated before entry into the study. Blood chemistries (to include total protein, albumin, calcium, phosphorus, glucose, BUN, creatinine, total bilirubin, alkaline phosphatase, AST, ALT) within 14 days of registration, as defined as follows: BUN < 25 mg; Creatinine < 1.5 mg; Total bilirubin < 1.5 mg/dL; ALT or AST < 2 x institutional upper limit of normal. Within 14 days prior to registration: Complete history and general physical examination; detailed neurological examination; documentation of steroid and anticonvulsant doses. Patients of reproductive potential must practice an effective method of birth control during and for 2 months after treatment; negative serum pregnancy test within 5 days prior to registration for females of child-bearing potential. The patient must sign a study-specific informed consent prior to study entry; if the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member.
|
| Treatment: |
Phase I
ARM 1: MGd 3 mg/kg
ARM 2: MGd 4 mg/kg
ARM 3: MGd 5 mg/kg
Phase II
ARM 4: MGd MTD of phase I
Radiation Therapy:
2.0 Gy x 30 fractions, 5 days/week x 6 weeks for a total dose of 60.0 Gy
Concurrent Motexafin Gadolinium (MGd) During Radiation Therapy:
--22 total doses at MTD of phase I portion of the study over 6 weeks
--Weeks 1 & 2, IV daily Mon-Fri 2-5 hrs before radiation therapy
--Weeks 3-6, IV Mon, Wed, Fri 2-5 hrs before radiation therapy
Concurrent Temozolomide During Radiation Therapy:
--Daily during radiation therapy, beginning the night before the first dose of radiation & ending the night before the last dose of radiation
Post-Radiation Temozolomide:
--Daily for 5 days every 28 days for 6 cycles, starting 28 days after the completion of radiation therapy
|
| Study size: | 113 |
| RTOG 0525 |
|---|
| Number: |
RTOG 0525 |
| Title: |
Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma |
| Eligibility: |
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. Neurologic examination within 14 days prior to study registration. Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration. Karnofsky performance status of > 60. Age > 18 years. 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. (Note: The use of transfusion or other intervention to achieve Hgb > 10 g/dl is acceptable.) Adequate renal function, as defined as: BUN < 25 mg/dl within 14 days prior to study registration; Creatinine < 1.7 mg/dl within 14 days prior to study registration. Adequate hepatic function, as defined as: Bilirubin < 2.0 mg/dl within 14 days prior to study registration; ALT < 3 x normal range within 14 days prior to study registration; AST < 3 x normal range within 14 days prior to study registration. Patients must sign a study-specific informed consent prior to study registration. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member. For females of child-bearing potential, negative serum pregnancy test within 72 hours prior to starting temozolomide. Women of childbearing potential and male participants must practice adequate contraception.
|
| 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.
|
| Study size: | 834 |
| 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.
|
|
|
| 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 0625 |
|---|
| Number: | RTOG 0625 |
| Title: |
A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma
|
| Eligibility: |
Histologically proven intracranial glioblastoma or gliosarcoma. There must be pathologic or imaging confirmation of tumor progression or regrowth. Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made. 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 glioblastoma trial do not need to consent to having their material re-reviewed by the central pathologist for this study. History and physical examination, including neurologic examination, within 8 weeks prior to registration. Systolic blood pressure < 160 mg Hg or diastolic pressure < 90 mg Hg. Patients must be able to undergo brain MRI scans with intravenous gadolinium. Unequivocal radiographic evidence for tumor progression by MRI as defined in Section 11.2.1.2 within 14 days prior to registration. Patients must be on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required. Karnofsky performance status > 70. Age > 18. CBC/differential obtained 14 days prior to registration, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) > 1,500/mm3; Platelets > 100,000 cells/mm3; Hemoglobin > 10.0 gm/dL (Note: The use of transfusion or other intervention to achieve Hgb > 10.0 is acceptable); White blood cell count (WBC) > 3,000/mcL. Adequate liver function within 14 days prior to registration, defined as follows: SGOT [AST] < 2 times the upper limit of normal; Bilirubin < 1.6 mg/dL. Adequate renal function within 14 days prior to registration, defined as follows: Creatinine < 1.5 mg/dL. 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. Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas: (1) [urine protein]/[urine creatinine]: if both protein and creatinine are reported in mg/dL; (2) [(urine protein) x0.088]/[urine creatinine]: if urine creatinine is reported in mmol/L. Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin. 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 (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin. Patients must have received prior temozolomide. Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of: 28 days from the administration of any investigational agent; 28 days from administration of prior cytotoxic therapy with the following exceptions: 14 days from administration of vincristine; 42 days from administration of nitrosoureas; 21 days from administration of procarbazine; 7 days from administration of non-cytotoxic agents [e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count)]. Patients having undergone recent resection of recurrent or progressive tumor must meet all of the following conditions: Patients must have recovered from the effects of surgery and a minimum of 28 days must have elapsed from the day of surgery to the day of registration. For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration. Residual disease following resection of recurrent glioblastoma is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be done no later than 96 hours in the immediate postoperative period or at least 4 weeks postoperatively, within 14 days prior to registration. If the "within 96-hour of surgery" scan is more than 14 days before registration, the scan needs to be repeated. Patients must have failed prior radiation therapy and must have an interval of > 42 days from the completion of radiation therapy to registration. Patients with prior therapy that included interstitial brachytherapy, Gliadel wafer, or stereotactic radiosurgery must have confirmation of true progressive disease, rather than radiation necrosis, based upon either PET or Thallium scanning, MRI spectroscopy, or surgical documentation of disease. Patients must sign study-specific informed consent prior to registration. Women of childbearing potential must have a negative ß-HCG pregnancy test documented within 14 days prior to registration. Women of childbearing potential and male participants must practice adequate contraception. The patient must agree to have standard of care MRIs submitted for review at a central repository.
|
| Treatment: |
Arm 1: Bevacizumab (q 2 weeks) plus temozolomide (days 1-21 of a 28-day cycle)
Arm 2: Bevacizumab (q 2 weeks) plus irinotecan (q 2 weeks) of a 28-day cycle
|
| Study size: | 121 |
| 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. 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. 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.
|
|
|
| Treatment: |
Dasatinib 100 mg BID |
| Study size: | 83 |
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| |
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