Ph. II Temozolomide + O6-BG in Treatment of Pts w Temozolomide-Resistant Malignant Glioma
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00613093 |
|
Recruitment Status :
Completed
First Posted : February 12, 2008
Last Update Posted : July 9, 2014
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Objectives:
To define role of O6-Benzylguanine (BG) in restoring Temodar (temozolomide) sensitivity in patients with Temodar-resistant malignant glioma.
To further define toxicity of combo therapy using Temodar + BG.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Multiforme Anaplastic Glioma | Drug: Temodar and O6-Benzylguanine (BG) | Phase 2 |
2 separate strata accrued independently of each other: Stratum 1-patients with Glioblastoma Multiforme (GBM). Stratum 2-patients with Anaplastic Glioma [anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed (AA and AO)] .
BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60 minutes of end of the 1-hour administration of BG infusion. Treatment cycles may be repeated every 28 days following dose of Temodar from previous cycle.
Temodar has been well tolerated by both adults and children with 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, hepatotoxicity, anorexia, fatigue and hyperglycemia. Hypersensitivity reactions have not yet been noted with Temodar. As in the case with many anti-cancer drugs, Temodar may be carcinogenic. BG toxicities include agitation, lethargy, nausea, vomiting, rapid heart rate, elevated liver functions, & leukemia; but, not with BG as single agent. Transient lymphopenia has been seen with BG as single agent.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 67 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Temodar-Resistant Malignant Glioma |
| Study Start Date : | October 2002 |
| Actual Primary Completion Date : | March 2006 |
| Actual Study Completion Date : | August 2008 |
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: Patients with glioblastoma multiforme |
Drug: Temodar and O6-Benzylguanine (BG)
Objectives of study are to define role of BG in restoring Temodar sensitivity in patients with Temodar-resistant malignant glioma and to further define the toxicity of combination therapy using Temodar + BG. 2 separate strata accrued independently of each other: Stratum 1-patients with glioblastoma multiforme (GBM). Stratum 2-patients with anaplastic glioma (AG). BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24 hours. Temodar 472mg/m2 administered orally, in fasting state, within 60 minutes of end of the 1-hour administration of BG infusion. Treatment cycles may be repeated every 28 days following dose of Temodar from previous cycle. Other Names:
|
| Active Comparator: Patients with Anaplastic Glioma |
Drug: Temodar and O6-Benzylguanine (BG)
Objectives of study are to define role of BG in restoring Temodar sensitivity in patients with Temodar-resistant malignant glioma and to further define the toxicity of combination therapy using Temodar + BG. 2 separate strata accrued independently of each other: Stratum 1-patients with glioblastoma multiforme (GBM). Stratum 2-patients with anaplastic glioma (AG). BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24 hours. Temodar 472mg/m2 administered orally, in fasting state, within 60 minutes of end of the 1-hour administration of BG infusion. Treatment cycles may be repeated every 28 days following dose of Temodar from previous cycle. Other Names:
|
- Radiographic evidence of tumor response [ Time Frame: 6 months ]
- 6 month progression-free survival [ Time Frame: 6 months ]
- Relationship between tumor AGT at original diagnosis & response to Temozolomide + O6-BG [ Time Frame: 6 months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients have recurrent/progressive Malignant Glioma (MG). Stereotactic biopsy at time of recurrence/progression is only required if radiation-induced necrosis is suspected
- Patients have MG resistant to Temodar, which is defined as > or = to 25 percent increase in tumor growth on contrast enhanced MRI/CT within 8 weeks of last dose of Temodar
- Age > or = to 18 years
- Evidence of measurable enhancing disease on contrast-enhanced MRI, unless medically contraindicated.
- Interval of at least 2 weeks between prior surgical resection/ 4 weeks between prior radiotherapy/chemotherapy, and enrollment on protocol unless there is unequivocal evidence of tumor progression. However, patients treated with chemotherapy agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if less than 4 weeks from last prior dose of chemotherapy
- Karnofsky performance score > or = to 60 percent
- Hematocrit > 29 percent, absolute neutrophil count (ANC) > 1,500 cells/microliter, platelets > 100,000 cells/microliter
- Serum creatinine <1.5 mg/dl, Blood Urea Nitrogen (BUN) <25 mg/dl, Serum Glutamic Oxaloacetic Transaminase (SGOT) & bilirubin <1.5 x upper limit of normal (ULN)
- For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, and dose should not be escalated over entry dose level
- Signed informed consent approved by Institutional Review Board (IRB) prior to patient entry
- If sexually active, patients will take contraceptive measures for duration of treatments
Exclusion criteria:
- Pregnancy
- Co-medication that may interfere with study results
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): NCT00613093
| United States, North Carolina | |
| Duke University Health System | |
| Durham, North Carolina, United States, 27710 | |
| Principal Investigator: | David A. Reardon, MD | Duke University Health System |
Additional Information:
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT00613093 History of Changes |
| Other Study ID Numbers: |
4260 |
| First Posted: | February 12, 2008 Key Record Dates |
| Last Update Posted: | July 9, 2014 |
| Last Verified: | November 2012 |
Keywords provided by Duke University:
|
Temodar Temozolomide O6-BG O6-Benzylguanine NSC 637037 Temodar-Resistant Malignant Glioma |
Brain tumor CNS tumor Cerebral glioblastoma Anaplastic astrocytomas Glioma |
Additional relevant MeSH terms:
|
Glioblastoma Glioma Astrocytoma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial |
Neoplasms, Nerve Tissue Temozolomide Dacarbazine O(6)-benzylguanine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors |