A Phase I Study of Continuous Oral Administration of SCH 66336 and 5-Fluorouracil/Leucovorin (5FU/LV) in Patients With Advanced Cancer
fluorouracil
+ leucovorin calcium
+ lonafarnib
Lymphadenopathy+35
+ Chronic Disease
+ DNA Virus Infections
Treatment Study
Summary
Study start date: April 1, 1999
Actual date on which the first participant was enrolled.OBJECTIVES: I. Determine the safety, tolerability, maximum tolerated dose, and dose limiting toxicity of oral SCH 66336 with fluorouracil and leucovorin calcium in patients with advanced malignancy. II. Assess the multiple dose pharmacokinetics of oral SCH 66336 when administered with fluorouracil and leucovorin calcium. III. Assess the pharmacokinetics of fluorouracil when administered with oral SCH 66336. IV. Assess antitumor activity of oral SCH 66336 with fluorouracil and leucovorin calcium in these patients. OUTLINE: This is a dose escalation study of SCH 66336. Patients receive oral SCH 66336 twice daily for 56 days. Patients receive leucovorin calcium IV over 1-2 minutes immediately followed by fluorouracil IV over 1-2 minutes on days 1, 8, 15, 22, 29, and 36. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SCH 66336. The maximum tolerated dose is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicity (DLT) during course 1, with at least 2 patients experiencing DLT at the next higher level. PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.25 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Histologically proven malignancy for which no curative therapy exists At least 1 bidimensionally measurable lesion No acute or chronic leukemia or multiple myeloma No active CNS metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG-WHO 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count greater than 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT or SGPT no greater than 3 times upper limit of normal (ULN) (5 times ULN if elevations due to liver metastasis) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No prior or concurrent QTc interval prolongation greater than 500 m/sec, unless approved by cardiology consult prior to study Other: No malabsorption syndrome due to surgery, prior disease, or other unknown reason No frequent vomiting or other medical condition that could interfere with oral medicine intake (e.g., partial bowel obstruction, external biliary diversion) No concurrent nonmalignant systemic disease making patient a poor risk for study No active uncontrolled infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy and recovered No prior allogeneic, syngeneic, or autologous bone marrow transplantation No prior peripheral blood stem cell transplantation No concurrent biologic therapy Chemotherapy: No more than 2 prior chemotherapy regimens At least 4 weeks since prior chemotherapy (6 weeks since mitomycin or nitrosoureas) and recovered No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No prior wide field radiation (radiotherapy to at least 25% of bone marrow, including pelvic irradiation) No concurrent radiotherapy Surgery: Prior major gastrointestinal surgery allowed if recovered Other: At least 4 weeks since other prior investigational therapy and recovered
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Memorial Sloan-Kettering Cancer Center
New York, United StatesOpen Memorial Sloan-Kettering Cancer Center in Google Maps