Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma
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|ClinicalTrials.gov Identifier: NCT01004874|
Recruitment Status : Active, not recruiting
First Posted : October 30, 2009
Results First Posted : January 18, 2013
Last Update Posted : April 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Malignant Glioma Glioblastoma Gliosarcoma||Drug: Bevacizumab Drug: Temozolomide Radiation: Radiation Therapy (XRT) Drug: Topotecan||Phase 2|
The primary objective of this study is to use 6-month progression-free survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objectives are to determine the overall survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan and to describe the toxicity of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan.
The study will have survival and toxicity endpoints. Patients will be treated with standard radiation therapy and daily temozolomide for 6 and a half weeks of radiation. Avastin will be administered every other week beginning a minimum of 28 days after the last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of radiation therapy, patients will have a MRI and if there is no evidence of disease progression, patients will receive 12 cycles of Avastin, temozolomide, and topotecan (beginning a minimum of 14 days after the last radiation treatment). Subjects will be identified by the investigator as those patients who have newly diagnosed grade 4 malignant glioma (glioblastoma multiforme or gliosarcoma), and be within 6 weeks of the last major surgical procedure, craniotomy, open biopsy, or stereotactic biopsy.
Fifty (50) patients will initially be accrued to the study and the overall efficacy of the treatment regimen assessed. Analyses will be conducted within subgroups defined by methylation status.
Early side effects of radiation that may start during radiation include hair loss, scalp redness, inflammation of the ear canals, and fatigue. There is a small chance of long-term effects from radiation, occurring after months or years after completion. These may include worsening of mental function, hearing, vision, strength and coordination. In initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. Temozolomide has been well tolerated by both adults and children with the most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, and hepatotoxicity. With topotecan, reversible myelosuppression with leukopenia and thrombocytopenia is dose limiting. Nausea and vomiting, as well as diarrhea and alopecia, are frequent. Moderate fatigue, transient elevation of hepatic transaminase levels, stomatitis, anemia, fever, mucositis, flu-like symptoms, and rash have been reported.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Avastin in Combination With Radiation and Temozolomide Followed by Avastin, Temozolomide, and Topotecan for Glioblastoma Multiformes and Gliosarcomas|
|Actual Study Start Date :||December 30, 2009|
|Actual Primary Completion Date :||July 2012|
|Estimated Study Completion Date :||December 2018|
Experimental: Bevacizumab, XRT, Temozolomide, Topotecan
Patients are treated with standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation. Following completion of radiation therapy, patients have a MRI and, if there is no evidence of disease progression, patients receive 12 cycles of Avastin, temozolomide, and topotecan. Beginning a minimum of 14 days after the last radiation treatment, the Avastin is dosed at 10 mg/kg every other week; temozolomide is given at 150 mg/m2 daily the first 5 days in combination with topotecan on days 2 through 6 at 1.5 mg/ m2 for patient not taking EIAEDs and 2.0 mg/ m2 for patients taking EIAEDs on days 2-6 of each 28-day.
Bevacizumab (Avastin) at 10 mg/kg every other week during standard radiation therapy (XRT). Following XRT, bevacizumab will remain at 10 mg/kg every other week.
Other Name: Avastin
Daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation therapy (XRT). Following XRT, temozolomide will be dosed at 150 mg/m2 daily the first 5 days of each 28-day cycle.
Other Name: Temodar
Radiation: Radiation Therapy (XRT)
Standard radiation therapy for approximately 6.5 weeks
Following standard radiation therapy, patients will receive topotecan on days 2 through 6 of each 28-day cycle at a dose of 1.5 mg/m2 for patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs) and 2.0 mg/m2 for patients taking EIAEDs.
Other Name: Hycamtin
- 6-month Progression-free Survival [ Time Frame: 6 months ]Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
- One and Two Year Overall Survival [ Time Frame: One year and two years ]Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date.
- Median Overall Survival [ Time Frame: 27 months ]OS was defined as time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
- Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage [ Time Frame: 27 months ]Number of times a CNS hemorrhage or systemic hemorrhage was experienced
- Number of Patients Experiencing a Greater Than or Equal to Grade 4 Hematologic or a Greater Than or Equal to Grade 3 Non-hematologic Toxicity [ Time Frame: 27 months ]Number of times a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity was experienced
- Median Progression-free Survival [ Time Frame: 27 months ]PFS was defined as time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01004874
|United States, North Carolina|
|The Preston Robert Tisch Brain Tumor Center at Duke|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD, FRCPC||Duke University|