Ph. I Temozolomide + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas
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Purpose
Objectives:
To determine maximum tolerated dose of CPT-11 when administered following Temodar plus O6-benzylguanine To characterize any toxicity associated w combo of CPT-11 + Temodar plus O6-BG To observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar + O6-BG
| Condition | Intervention | Phase |
|---|---|---|
| Glioblastoma Gliosarcoma | Drug: Temodar, O6-BG, and Irinotecan | Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | Phase I Trail of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) Plus Irinotecan (CPT-11) (NSC 616348) in the Treatment of Patients With Recurrent / Progressive Cerebral Anaplastic Gliomas |
- Incidence of toxicities [ Time Frame: 6 months ]
- Response rate & progression-free survival [ Time Frame: 6 months ]
| Estimated Enrollment: | 96 |
| Study Start Date: | January 2005 |
| Study Completion Date: | July 2008 |
| Primary Completion Date: | January 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
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Experimental: 1
Pts receiving Dilantin, Tegretol or Phenobarbital
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Drug: Temodar, O6-BG, and Irinotecan
2 separate strata accrued independently: Stratum 1-pts receiving Dilantin, Tegretol or phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. O6-BG administered intravenously 120mg/m2, over 1hr, prior to administration of Temozolomide on day 1 of 21day cycle. O6-BG administered intravenously 30mg/m2/day, over 48hrs, immediately after completion of CPT-11 infusion on day 1 of 21-day cycle. Temozolomide administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temozolomide from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60mg/m2 for stratum 1 & 40mg/m2 for stratum2. Treatment cycles repeated every 3 wks following dose of CPT-11 from previous cycle.
Other Names:
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Experimental: 2
Pts on anti-convulsants other than Dilantin, Tegretol / Phenobarbital / pts not on any anti-convulsants
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Drug: Temodar, O6-BG, and Irinotecan
2 separate strata accrued independently: Stratum 1-pts receiving Dilantin, Tegretol or phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. O6-BG administered intravenously 120mg/m2, over 1hr, prior to administration of Temozolomide on day 1 of 21day cycle. O6-BG administered intravenously 30mg/m2/day, over 48hrs, immediately after completion of CPT-11 infusion on day 1 of 21-day cycle. Temozolomide administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temozolomide from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60mg/m2 for stratum 1 & 40mg/m2 for stratum2. Treatment cycles repeated every 3 wks following dose of CPT-11 from previous cycle.
Other Names:
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Detailed Description:
Objectives of study: to determine maximum tolerated dose of CPT-11 when administered following Temodar + O6-benzylguanine (O6-BG); to characterize any toxicity associated w combo of CPT-11 + Temodar + O6-BG; to observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar plus O6-BG. Pts have histologically confirmed diagnosis of recurrent primary malignant glioma. 2 separate strata accrued independently of each other: Stratum 1-pts receiving Dilantin, Tegretol/phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. Each strata will be treated & escalated independent of each other.
Pre-chemo, O6-BG administered intravenously at 120 mg/m2, over 1hr, prior to administration of Temodar on day 1 of 21-day cycle. Post-chemo, O6-BG administered intravenously at 30 mg/m2/day, over 48hrs, immediately after completion of the CPT-11 infusion on day 1 of 21-day cycle. Temodar administered orally at 355 mg/m2, in fasting state, within 60 minutes of the end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3 weeks following dose of Temozolomide from previous cycle. CPT-11 will be administered intravenously in fasting state over 90min. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60 mg/m2 for stratum 1 & 40 mg/m2 for stratum 2. Treatment cycles may be repeated every 3 wks following dose of CPT-11 from previous cycle.
Major toxicities associated w CPT- 11 are myelosuppression & diarrhea. Temozolomide has been well tolerated by both adults & children w most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea & vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, & hepatotoxicity. Hypersensitivity reactions have not yet been noted w Temozolomide. As is case w many anti-cancer drugs, Temozolomide may be carcinogenic. O6-BG toxicities include transient lymphopenia has been seen w O6-BG as single agent. O6-BG in combo w other agents could cause exacerbation of any adverse event currently known to be caused by other agent,/ combo may result in events never previously associated w either agent. Animal studies indicated that agitation, lethargy, convulsions, nausea, vomiting, rapid heart rate, elevated liver functions, leukopenia, lymphopenia could be seen.
Eligibility
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Pts have histologically confirmed diagnosis of recurrent primary malignant glioma
- Age >18yrs
- Evidence of measurable recurrent/residual primary CNS neoplasm on contrast-enhanced MRI, unless medically contraindicated
- An interval of >2 wks between prior surgical resection/6 wks between prior XRT/chemo, & enrollment on protocol, unless there is unequivocal evidence of tumor progression after surgery, XRT/chemo
- KPS>60 percent
- Adequate hematologic, renal & liver function as demonstrated by lab values performed within 14 days, inclusive, prior to administration of chemo:
- ANC >1500/mm3
- Platelet count > 00,000/mm3
- Hemoglobin > 10gm/dL
- BUN & serum creatinine <1.5 x ULN
- Total serum bilirubin <1.5 x ULN
- SGOT & SGPT < 2.5 x ULN
- Alkaline phosphatase of< 2 x ULN
- Pts must have recovered from any effects of major surgery.=
- Pts must have life expectancy of >12wks
- Pts/legal guardian must give written, informed consent
Exclusion Criteria:
- Pts requiring immediate XRT
- Pts have not recovered from surgery
- Pts are not neurologically stable for 2wks prior to study entry
- Pts are poor medical risks because of non-malignant systemic disease as well as those w acute infection treated w intravenous antibiotics
- Frequent vomiting/medical condition that could interfere w oral medication intake
- Previous active malignancy treated in past year except for localized in-situ carcinomas & basal/squamous cell carcinoma of skin
- Known HIV positivity/AIDS-related illness
- Pregnant/nursing women
- Women of childbearing potential who are not using effective method of contraception. Women of childbearing potential must have negative serum pregnancy test 24 hrs prior to administration of study drug & be practicing medically approved contraceptive precautions
- Men who are not advised to use effective method of contraception
- Prior failure of CPT-11
- Pts taking immuno-suppressive agents other than prescribed corticosteroids
Contacts and Locations
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): NCT00612638
| United States, North Carolina | |
| Duke University Health System | |
| Durham, North Carolina, United States, 27710 | |
| Principal Investigator: | David A. Reardon, MD | Duke University Health System |
More Information
Additional Information:
| Responsible Party: | David A. Reardon, MD, Duke University Health System |
| ClinicalTrials.gov Identifier: | NCT00612638 History of Changes |
| Other Study ID Numbers: |
Pro00007681 |
| First Submitted: | January 29, 2008 |
| First Posted: | February 12, 2008 |
| Last Update Posted: | June 19, 2013 |
| Last Verified: | January 2009 |
Keywords provided by Duke University:
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Temodar Temozolomide O6-Benzylguanine O6-BG NSC 637037 |
Irinotecan CPT-11 Recurrent cerebral anaplastic glioma Progressive cerebral anaplastic glioma Malignant glioma |
Additional relevant MeSH terms:
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Glioblastoma Glioma Gliosarcoma Astrocytoma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Irinotecan Camptothecin Temozolomide O(6)-benzylguanine |
Dacarbazine Phenobarbital Carbamazepine Phenytoin Anticonvulsants Convulsants Antineoplastic Agents, Phytogenic Antineoplastic Agents Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents Hypnotics and Sedatives |