RATIONALE: Drugs used in chemotherapy, such as SB-715992, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of SB-715992 in treating patients with metastatic or unresectable solid tumors or Hodgkin's or non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult Hodgkin's lymphoma adult lymphomatoid granulomatosis adult non-Hodgkin's lymphoma adult solid tumor indolent or aggressive adult non-Hodgkin's lymphoma	Drug: SB-715992  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of SB-715992 in patients with metastatic or unresectable solid tumor or Hodgkin's or non-Hodgkin's lymphoma.
• Determine the safety and tolerability of this drug in these patients.

Secondary

• Determine clinical response in patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Determine drug metabolism and biomarkers of efficacy of this drug in these patients.
• Determine the toxicity of this drug in these patients.
• Determine the potential interaction of the study drug with other drugs in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive SB-715992 IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SB-715992 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 additional patients are treated at the MTD

Patients are followed for 4 weeks.

PROJECTED ACCRUAL: A total of 18-31 patients will be accrued for this study within 11-19 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy of 1 of the following types:
• Solid tumor
• Hodgkin's or non-Hodgkin's lymphoma
• Bone marrow assessment must have been performed within the past 6 weeks
• Metastatic or unresectable disease
• Standard curative or palliative therapy does not exist or is no longer effective
• No known symptomatic or untreated brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior immunotherapy
• No concurrent colony-stimulating factors (CSFs) during the first course of study drug administration
• No concurrent prophylactic CSFs
• No concurrent anticancer biologic therapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Male patients receiving treatment for prostate cancer must continue luteinizing hormone-releasing hormone agonist therapy to maintain castrate levels of testosterone
• Concurrent hormone replacement therapy allowed
• Concurrent megestrol for supportive care allowed provided started ≥ 1 month before study entry
• No concurrent dexamethasone
• No concurrent anticancer hormonal therapy

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to ≥ 50% of total marrow volume
• No concurrent anticancer radiotherapy

Surgery

• Not specified

Other

• Recovered from all prior therapy
• More than 4 weeks since prior epidermal growth factor receptor inhibitors
• More than 7 days since prior and no concurrent grapefruit juice
• More than 14 days since prior and no concurrent moderate to significant inhibitors or inducers of CYP3A4, including the following:
• Clarithromycin
• Erythromycin
• Troleandomycin
• Itraconazole
• Ketoconazole
• Fluconazole (dose > 200 mg/day)
• Voriconazole
• Nefazodone
• Fluvoxamine
• Verapamil
• Diltiazem
• Bitter orange
• Phenytoin
• Carbamazepine
• Phenobarbital
• Rifampin
• Rifabutin
• Rifapentine
• Hypericum perforatum (St. John's wort)
• Modafinil
• Oxcarbazepine
• No other investigational agents within 28 days before, during, and for at least 14 days after study treatment
• More than 6 months since prior and no concurrent amiodarone
• Concurrent bisphosphonates for supportive care allowed provided started ≥ 1 month before study entry
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent cytotoxic anticancer therapy
• No other concurrent anticancer therapy
• No concurrent use of any of the following:
• Ajmaline
• Cimetidine
• Clotrimazole
• Cyclosporine
• Fluoxetine
• Indinavir
• Nelfinavir
• Paroxetine
• Quinidine
• Ritonavir
• Saquinavir
• Sertraline

Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting

Study chairs or principal investigators

Patricia M. LoRusso, DO,  Study Chair,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000404369; WSU-C-2818; NCI-6785; NCT00101244
Record last reviewed:  March 2005
Last Updated:  March 15, 2005
Record first received:  January 7, 2005
ClinicalTrials.gov Identifier:  NCT00101244
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08