Ph. I Temo + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas - Full Text View

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 I

Drug Information available for:

Temozolomide Irinotecan Irinotecan hydrochloride O(6)-Benzylguanine Carbamazepine Phenytoin Phenytoin sodium Phenobarbital Phenobarbital sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study

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

Further study details as provided by Duke University:

Primary Outcome Measures:

Incidence of toxicities [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate & progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	96
Study Start Date:	January 2005
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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 Temo 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. Temo administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temo from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temo 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: Experimental 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 Temo 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. Temo administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temo from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temo 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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612638

Locations


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

Sponsors and Collaborators

Duke University

AOI Pharma, Inc.

Pharmacia

Investigators


Principal Investigator:	Jennifer A. Quinn, MD	Duke University Health System

More Information

The Preston Robert Tisch Brain Tumor Center at DUKE This link exits the ClinicalTrials.gov site

Responsible Party:	Duke University Health System ( Jennifer A. Quinn, MD )
Study ID Numbers:	4883
First Received:	January 29, 2008
Last Updated:	May 4, 2008
ClinicalTrials.gov Identifier:	NCT00612638
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

Study placed in the following topic categories:

Glioblastoma

Phenobarbital

Astrocytoma

Irinotecan

Temozolomide

Recurrence

Phenytoin

Neuroectodermal Tumors

Carbamazepine

Neoplasms, Germ Cell and Embryonal

Neuroepithelioma

O(6)-benzylguanine

Glioma

Gliosarcoma

Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms

Neoplasms by Histologic Type

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Therapeutic Uses

Neoplasms, Nerve Tissue

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Neoplasms, Neuroepithelial

Antineoplastic Agents, Phytogenic

Alkylating Agents

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 23, 2008

Sponsors and Collaborators:	Duke University AOI Pharma, Inc. Pharmacia
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00612638