PH I Addition of Farnesyl Transferase Inhibitor to Temozolomide for Pts w Gr 3 & 4 Malignant Gliomas

NCT00612651 | Completed Phase 1 DMC

• 2 other identifiers: Pro000050277009/Pro00005027
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: To determine maximum tolerated dose of farnesyl transferase inhibitor, SCH 66336, when administered w TEMODAR®. To characterize any toxicity associated w combo of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®. To observe patients for clinical antitumor response when treated with combination of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®. To assess pharmacokinetics of SCH 66336 for patients on \& not on enzyme inducing antiepileptic drugs.

Conditions

Gliosarcoma; Glioblastoma; Anaplastic Astrocytoma

Keywords

GBM; Malignant glioma; Brain tumor; Temodar; Temozolomide; SCH 66336; Farnesyl transferase inhibitor; Glioblastoma multiforme; Gliosarcoma; Anaplastic astrocytoma; Anaplastic oligodendroglioma; Anaplastic oligoastrocytoma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  6 months

Secondary Outcomes (1)

• Progression-free survival

  6 months

Study Arms (2)

enzyme-inducing anti-epileptic drugs (EIAEDs)

OTHER

Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs)such as carbamazepine, phenobarbitol, phenytoin, phosphenytoin, oxcarbamazepine, primadone)

Drug: Temodar and SCH 66336

no enyzme-inducing anti-epileptic drugs

OTHER

Patients on non CYP3A4-inducing anti-convulsants or patients not on any anti-convulsants.

Drug: Temodar and SCH 66336

Interventions

Temodar and SCH 66336 DRUG

2 separate strata accrued independently: Stratum 1-pts receiving CYP3A4-inducing anticonvulsants. Stratum 2-pts on non CYP3A4-inducing anticonvulsants or pts not on any anti-convulsants. Each strata treated \& escalated independent of each other. Temozolomide administered orally at dose of 150 mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200 mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles repeated every 4wks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice daily, approximately every 12hrs. Except as specifically noted, pts advised to take capsules wh morning \& evening meals, with approximately 240ml of non-carbonated water. Initial doses will be 125mg BID for stratum 1 \& 75mg BID for stratum2. Treatment cycles repeated every 4 wks following dose of Temozolomide from previous cycle.

Also known as: Temodar-Temozolomide, Farnesyl transferase inhibitor-SCH 66336

enzyme-inducing anti-epileptic drugs (EIAEDs); no enyzme-inducing anti-epileptic drugs

Eligibility Criteria

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

You may qualify if:

• Pts with MG histologically confirmed at diagnosis, who were treated previously with conventional external beam radiation \& with or without chemotherapy, \& have stable disease, recurrence or relapse at the time of enrollment.
• Age \> or = to 18 years.
• Patients who have had previous surgical resection(s) are eligible.
• Interval of at least 3 weeks between prior surgical resection, 2 weeks between prior radiotherapy, or 4 weeks between prior chemotherapy, unless there is unequivocal evidence of tumor progression after surgery, radiotherapy, or chemotherapy.
• Karnofsky performance score \> or = to 60%.
• Adequate hematologic, renal \& liver function as demonstrated by lab values performed within 14 days, inclusive, prior to administration of chemotherapy:
• ANC \> or = to 1500/mm3
• Platelet count \> or = to 100,000/mm3
• Hemoglobin \> or = to 10 gm/dL
• BUN and serum creatinine \<1.5 times upper limit of lab normal
• Total serum bilirubin \<1.5 times upper limit of lab normal
• SGOT \<2.5 times upper limit of lab normal
• Patients must have recovered from any effects of major surgery.
• Patients must have life expectancy of greater than 12 weeks.
• Patients or legal guardian must give written, informed consent.

You may not qualify if:

• Patients requiring immediate radiation therapy.
• Patients who have not recovered from surgery.
• Patients who are not neurologically stable for 2 weeks prior to study entry.
• Patients who are poor medical risks because of non-malignant systemic disease as well as those with acute infection treated with intravenous antibiotics.
• Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
• Patient is \< 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Known HIV positivity or AIDS-related illness.
• Pregnant or nursing women.
• Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 72 hours prior to administration of study drug and be practicing medically approved contraceptive precautions.
• Men who are not advised to use an effective method of contraception.
• Patients taking immuno-suppressive agents other than prescribed corticosteroids.
• Patients previously treated with farnesyl transferase inhibitors.
• Patients with significant QTc prolongation (\>500 msec)as evaluated by an EKG.
• Patients having presented prior disease progression on TEMODAR.
• Patients having presented any grade 4 hematologic toxicity or grade 3 or 4 non-hematologic toxicity on TEMODAR in the past.

Sponsors & Collaborators

• Duke University: lead
• Schering-Plough: 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

Gliosarcoma; Glioblastoma; Astrocytoma; Glioma; Brain Neoplasms; Oligodendroglioma

Interventions

Temozolomide; lonafarnib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Annick Desjardins, 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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: October 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: June 1, 2011
• Last Updated: February 20, 2013

Record last verified: 2013-02

Locations

US (1)