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

NCT00612638 | Completed Phase 1 DMC

• 1 other identifier: Pro00007681
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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

Conditions

Glioblastoma; Gliosarcoma

Keywords

Temodar; Temozolomide; O6-Benzylguanine; O6-BG; NSC 637037; Irinotecan; CPT-11; Recurrent cerebral anaplastic glioma; Progressive cerebral anaplastic glioma; Malignant glioma

Outcome Measures

Primary Outcomes (1)

• Incidence of toxicities

  6 months

Secondary Outcomes (1)

• Response rate & progression-free survival

  6 months

Study Arms (2)

1

EXPERIMENTAL

Pts receiving Dilantin, Tegretol or Phenobarbital

Drug: Temodar, O6-BG, and Irinotecan

2

EXPERIMENTAL

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

Drug: Temodar, O6-BG, and Irinotecan

Interventions

Temodar, O6-BG, and Irinotecan 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.

Also known as: Temodar-Temozolomide, O6-Benzylguanine-O6-BG, Irinotecan-Camptosar-CPT 11

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Keryx / AOI Pharmaceuticals, Inc.: collaborator
• Pharmacia: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma

Interventions

Temozolomide; O(6)-benzylguanine; Irinotecan

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• David A. Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: January 1, 2005
• Primary Completion: January 1, 2007
• Study Completion: July 1, 2008
• Last Updated: June 19, 2013

Record last verified: 2009-01

Locations

US (1)