Brain/Spinal Cord Cancers
|Recruiting||Astrocytomas; Brain Cancer; Central Nervous System (CNS); Glioblastoma Multiforme; Solid Tumors||Phase II||
A randomized study comparing the safety and efficacy of weekly PPX infusions during radiation therapy versus the standard treatment of daily oral Temozolomide during radiation therapy. The current standard of care for patients with GBM, regardless of MGMT methylation, is temozolomide and concurrent radiation. PPX is a powerful radiation enhancer. GBM without MGMT methylation represents the ideal disease site to evaluate a new radiation sensitizer. This subset of patients have inferior survival as compared to patients with MGMT methylation and this variable is being used as a stratification variable and/or eligibility criteria in the phase III RTOG and EMD Serono trials, respectively. Since temozolomide does not statistically improve outcome in patients without MGMT methylation, it does not need to be administered in the investigational PPX arm so there will be no concern about drug interaction. However, temozolomide will be used in both arms following initial chemoradiation. This will be a randomized phase II study. Patients with GBM without MGMT Methylation undergo 2:1 randomization to the investigational arm, PPX/RT, versus the standard arm temozolomide/RT, respectively. The primary endpoint point of the randomized phase II study will be PFS. The information from this study will be utilized to plan a phase III trial.
- Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV)
- GBM must have unmethylated MGMT as determined by central laboratory
- Diagnosis of GBM must be made by biopsy or surgical excision, either partial or complete; as long as there is sufficient tissue to determine MGMT status
- No prior chemotherapy or radiation for brain tumor
Must be able to tolerate brain MRIs.
*A diagnostic contrast-enhanced MRI must be performed postoperatively within 42 days prior to study registration.
- KPS >60.
- Age > 18
- Life expectancy of at least 3 months.
- Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm,
- Creatinine < 2 x ULN
- ALT or AST < 3 x upper limit of normal (ULN) and total bilirubin < 1.5x ULN.
- Patients with a prior history of low grade glioma who did not receive prior radiation or chemotherapy with transformation to grade IV brain tumor are eligible.
- Women must be non-lactating, and surgically sterile, post-menopausal or have a negative serum pregnancy test and agree to use adequate birth control. Males must agree to use adequate birth control.
- Voluntary, signed informed consent.
- Acute infection or other medical condition that would impair study treatment
- No other active invasive malignancy unless disease free for at least 3 years.
- Prior temozolomide or PPX.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
- Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
- No diffuse leptomeningeal disease, or gliomatosis cerebri.
- Use of any other experimental chemotherapy drug within the 60 days prior to randomization and during the trial. (Use of a non-chemotherapy investigational agent must be approved by the Brown University Oncology Group)
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
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