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

NCT ID: NCT00612638

Last Updated: 2013-06-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2008-07-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Glioblastoma Gliosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Pts receiving Dilantin, Tegretol or Phenobarbital

Group Type EXPERIMENTAL

Temodar, O6-BG, and Irinotecan

Intervention Type DRUG

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.

2

Pts on anti-convulsants other than Dilantin, Tegretol / Phenobarbital / pts not on any anti-convulsants

Group Type EXPERIMENTAL

Temodar, O6-BG, and Irinotecan

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Temodar-Temozolomide O6-Benzylguanine-O6-BG Irinotecan-Camptosar-CPT 11

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Keryx / AOI Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Pharmacia

INDUSTRY

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Duke University Health System

Principal Investigators

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David A. Reardon, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

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Duke University Health System

Durham, North Carolina, United States

Site Status

Countries

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United States

Related Links

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http://www.cancer.duke.edu/btc/

The Preston Robert Tisch Brain Tumor Center at DUKE

Other Identifiers

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Pro00007681

Identifier Type: -

Identifier Source: org_study_id

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