Clinical trial NCT00003956: Combination Chemotherapy in Treating Patients With Advanced Cancer
Official title: A Phase I Study of Continuous Oral Administration of SCH 66336 and 5-Fluorouracil/Leucovorin (5FU/LV) in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
unspecified adult solid tumor, protocol specific
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-09-14
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of SCH 66336, fluorouracil, and leucovorin in treating patients who have advanced cancer.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Leonard B. Saltz, MD
role: STUDY_CHAIR
References: