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 Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: 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 ] [ Designated as safety issue: No ]
- Response rate & progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
| 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 |
|---|---|
|
Experimental: 1
Pts receiving Dilantin, Tegretol or Phenobarbital
|
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
|
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| 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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: 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 |
| Study First Received: | January 29, 2008 |
| Last Updated: | June 18, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Duke University:
|
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 Phenytoin Carbamazepine Phenobarbital Anticonvulsants Convulsants Antineoplastic Agents, Phytogenic Antineoplastic Agents Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents Voltage-Gated Sodium Channel Blockers |
ClinicalTrials.gov processed this record on September 23, 2016