Ph. I Temo + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas
Information source: Duke University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Glioblastoma; Gliosarcoma
Intervention: Temodar, O6-BG, and Irinotecan (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: Duke University Official(s) and/or principal investigator(s):
Jennifer A. Quinn, MD, Principal Investigator, Affiliation: Duke University Health System
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
Clinical Details
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 design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study
Primary outcome: Incidence of toxicities
Secondary outcome: Response rate & progression-free survival
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 Temo from previous cycle. CPT-11 will be administered intravenously in fasting state
over 90min. CPT-11 infusion will begin 1hr after Temo 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 Temo. As is case w many
anti-cancer drugs, Temo 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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Duke University Health System, Durham, North Carolina 27710, United States
Additional Information
The Preston Robert Tisch Brain Tumor Center at DUKE
Starting date: January 2005
Ending date: January 2015
Last updated: May 4, 2008
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