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

• Status: Completed
• Trial end date: 2011-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: Schering-Plough
• Treatments: Anticonvulsants; Dacarbazine; Lonafarnib; Temozolomide

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.