Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas - Full Text View

Sponsored by:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00083096

Purpose

RATIONALE: Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving lonafarnib together with temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with temozolomide in treating patients with recurrent primary supratentorial glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: lonafarnib Drug: temozolomide	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Lonafarnib

U.S. FDA Resources

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

Primary Outcome Measures:

Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response (complete [CR] or partial response [PR]) measured by McDonald's criteria at least 4 weeks after first documented response and every 8 weeks until disease progression or until start of another treatment [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	March 2004
Estimated Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose and dose-limiting toxicity of lonafarnib when administered with temozolomide in patients with recurrent primary supratentorial gliomas.
Determine the safety and tolerability of this regimen in these patients.

Secondary

Determine the mechanism of action of lonafarnib in these patients.
Determine the pharmacodynamics and pharmacokinetics of this regimen in these patients.
Determine the activity of this regimen in these patients.
Determine the response to this regimen in patients who have measurable disease.

OUTLINE: This is a nonrandomized, multicenter, open-label, dose-escalation study of lonafarnib.

Patients receive oral temozolomide once daily on days 2-6 of course 1 and on days 1-5 of all subsequent courses.

Patients also receive oral lonafarnib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of lonafarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experience dose-limiting toxicity. An additional 3 patients may be treated at the highest dose level achieved.

Patients are followed every 8 weeks for 6 months and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary supratentorial glioma
- Multifocal disease allowed
Recurrent disease after prior surgery and/or radiotherapy
Radiological evidence of increased and/or enhanced target lesion
Amenable to temozolomide therapy

PATIENT CHARACTERISTICS:

Age

Over 18

Performance status

ECOG 0-2 OR
WHO 0-2

Life expectancy

Not specified

Hematopoietic

Neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10.0 g/dL

Hepatic

Alkaline phosphatase < 2.5 times upper limit of normal (ULN)
Transaminases < 2.5 times ULN
Bilirubin < 1.5 times ULN

Renal

Creatinine < 1.7 mg/dL

Cardiovascular

Cardiac function clinically normal
Normal 12-lead ECG
QTc ≤ 440 msec on ECG
No ischemic heart disease within the past 6 months

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
No unstable systemic disease
No active uncontrolled infection
No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
No other active or recurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent anticancer biologic agents

Chemotherapy

At least 4 weeks since prior chemotherapy (6 weeks for temozolomide)
Prior adjuvant chemotherapy allowed
No more than 1 prior chemotherapy regimen for recurrent disease
No other concurrent chemotherapy

Endocrine therapy

Concurrent corticosteroids allowed provided treatment remains at a stable or decreasing dose for at least 2 weeks

Radiotherapy

See Disease Characteristics
No concurrent radiotherapy

Surgery

See Disease Characteristics
At least 3 months since prior surgery for primary brain tumor

Other

Concurrent anticonvulsants allowed
No other concurrent anticancer agents
No other concurrent investigational therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083096

Locations

France
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Regional Rene Gauducheau
Nantes-Saint Herblain, France, 44805
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Study Chair:	Mario Campone, MD	Centre Regional Rene Gauducheau
Study Chair:	Roger Stupp, MD	Centre Hospitalier Universitaire Vaudois

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000362066, EORTC-16027, EORTC-26023, SPRI-P03174
Study First Received:	May 14, 2004
Last Updated:	July 9, 2009
ClinicalTrials.gov Identifier:	NCT00083096 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult brain tumor
adult mixed glioma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult glioblastoma
adult pilocytic astrocytoma
adult anaplastic ependymoma
adult subependymoma

adult myxopapillary ependymoma
adult oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
adult diffuse astrocytoma
adult subependymal giant cell astrocytoma
adult pineal gland astrocytoma

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Temozolomide
Ependymoma
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Oligodendroglioma
Antineoplastic Agents, Alkylating
Glioma
Gliosarcoma
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Nervous System Diseases
Central Nervous System Neoplasms
Temozolomide
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms

Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Antineoplastic Agents, Alkylating
Glioma
Neoplasms, Neuroepithelial
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 03, 2009