Ph. I Temozolomide + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment	Phase
Glioblastoma; Gliosarcoma	Drug: Temodar, O6-BG, and Irinotecan	Phase 1

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.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	96 participants
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
Study Start Date :	January 2005
Actual Primary Completion Date :	January 2007
Actual Study Completion Date :	July 2008

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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: Temodar-Temozolomide; O6-Benzylguanine-O6-BG; Irinotecan-Camptosar-CPT 11
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: Temodar-Temozolomide; O6-Benzylguanine-O6-BG; Irinotecan-Camptosar-CPT 11

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Incidence of toxicities [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Response rate & progression-free survival [ Time Frame: 6 months ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Keryx / AOI Pharmaceuticals, Inc.

Pharmacia

Investigators

Principal Investigator:	David A. Reardon, MD	Duke University Health System

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The Preston Robert Tisch Brain Tumor Center at DUKE 

Responsible Party:	David A. Reardon, MD, Duke University Health System
ClinicalTrials.gov Identifier:	NCT00612638 History of Changes
Other Study ID Numbers:	Pro00007681
First Posted:	February 12, 2008
Last Update Posted:	June 19, 2013
Last Verified:	January 2009

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:

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