Irinotecan Plus Radiation Therapy Followed By Chemotherapy in Treating Patients With Glioblastoma Multiforme - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00027612

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Irinotecan may make the tumor cells more sensitive to radiation therapy.

PURPOSE: This phase I/II trial is studying the side effects of irinotecan given together with radiation therapy followed by irinotecan and carmustine and to see how well it works in treating patients with newly-diagnosed glioblastoma multiforme.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: carmustine Drug: irinotecan hydrochloride Procedure: adjuvant therapy Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Pilot And Phase II Trial Of Irinotecan And Radiation Followed By Irinotecan And BCNU In Glioblastoma Multiforme Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Irinotecan U 101440E Irinotecan hydrochloride Carmustine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Survival at 52 weeks [ Designated as safety issue: No ]

Study Start Date:	July 2002
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the safety of adjuvant irinotecan when administered concurrently with radiotherapy in patients with newly diagnosed glioblastoma multiforme.
Determine survival of patients treated with this regimen followed by irinotecan and carmustine.
Assess the toxic effects of this regimen in these patients.
Determine whether the dose of irinotecan chosen produces radiosensitizing plasma concentrations of SN-38 in these patients.
Assess individual variation in responses (toxicity and/or activity), pharmacokinetic parameters, and/or biological correlates due to genetic differences in enzymes involved in transport, metabolism, and/or mechanism of action of irinotecan in these patients treated with this regimen.

OUTLINE: This is a pilot, dose-escalation study of irinotecan. Patients are stratified according to receipt of concurrent enzyme-inducing anticonvulsants (EIACs) (yes vs no).

Phase I (closed to accrual as of 3/5/2005): Patients receive carmustine IV over 2 hours on day 1 of courses 2-5 and irinotecan IV over 90 minutes (beginning immediately after carmustine infusion) on days 1, 8, 22, and 29 of courses 1-5. Patients also undergo radiotherapy 5 days a week for 6 weeks concurrently with course 1 only. Treatment repeats every 6 weeks for 5 courses in the absence of unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of irinotecan until the recommended dose for phase II is determined. The recommended dose for phase II is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity.

Phase II (patients receiving concurrent EIACs or non-EIACs open to accrual as of 3/5/2005): Patients receive irinotecan at the recommended dose, carmustine, and cranial irradiation as in phase I.

Patients with disease progression are followed every 3 months for 5 years and then annually for up to 10 years.

Patients taken off study for reasons other than disease progression are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 12-48 patients (6-24 per stratum) will be accrued for phase I within 2-4 months (phase I closed to accrual as of 3/5/2005). A total of 93 patients will be accrued for phase II (open to accrual for patients receiving concurrent enzyme-inducing anticonvulsants [EIACs] or non-EIACs as of 3/5/2005).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed newly diagnosed grade IV astrocytoma or gliosarcoma
No oligodendrogliomas/oligoastrocytomas
Study entry must occur within 8 weeks after surgery

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 130,000/mm^3

Hepatic:

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
SGOT ≤ 2 times ULN

Renal:

Creatinine ≤ 0.5 mg/dL above ULN

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled infection
No other concurrent malignant disease except superficial skin cancers
No other major medical problems

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy for any tumor

Surgery:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027612

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Kurt A. Jaeckle, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Jaeckle KA, Ballman KV, Schomberg P: N997D: pilot trial of CPT11 during RT followed by CPT11 and BCNU in newly diagnosed glioblastoma (GBM) patients: a North Central Cancer Group (NCCTG) study. [Abstract] J Clin Oncol 23 (Suppl 16): A-1514, 117s, 2005.

Study ID Numbers:	CDR0000069048, NCCTG-N997D
Study First Received:	December 7, 2001
Last Updated:	July 14, 2009
ClinicalTrials.gov Identifier:	NCT00027612 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:

Glioblastoma
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Irinotecan
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Glioma
Alkylating Agents
Nervous System Neoplasms
Neoplasms by Histologic Type

Astrocytoma
Nervous System Diseases
Carmustine
Enzyme Inhibitors
Camptothecin
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009