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

This study has been completed.
Sponsor:
Collaborators:
Keryx / AOI Pharmaceuticals, Inc.
Pharmacia
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT00612638
First received: January 29, 2008
Last updated: June 18, 2013
Last verified: January 2009
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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
Study Completion Date: July 2008
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Keryx / AOI Pharmaceuticals, Inc.
Pharmacia
Investigators
Principal Investigator: David A. Reardon, MD Duke University Health System
  More Information

Additional Information:
No publications provided

Responsible Party: David A. Reardon, MD, Duke University Health System
ClinicalTrials.gov Identifier: NCT00612638     History of Changes
Other Study ID Numbers: Pro00007681
Study First Received: January 29, 2008
Last Updated: June 18, 2013
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

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Irinotecan
O(6)-benzylguanine
Phenobarbital
Temozolomide
Alkylating Agents
Anticonvulsants
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents

ClinicalTrials.gov processed this record on October 21, 2014