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

June 18, 2013 updated by: Duke University

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

96

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of toxicities
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Response rate & progression-free survival
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Pharmacia
Keryx / AOI Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

January 1, 2007

Study Completion (Actual)

July 1, 2008

Study Registration Dates

First Submitted

January 29, 2008

First Submitted That Met QC Criteria

February 11, 2008

First Posted (Estimate)

February 12, 2008

Study Record Updates

Last Update Posted (Estimate)

June 19, 2013

Last Update Submitted That Met QC Criteria

June 18, 2013

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00007681

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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