RATIONALE: Drugs used in chemotherapy use different ways to stop tumor 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 combining ZD0473 and doxorubicin in treating patients who have advanced solid tumors or lymphoma.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Eye Cancer	Procedure: chemotherapy  Drug: doxorubicin HCl liposome  Drug: ZD0473	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of ZD0473 and doxorubicin HCl liposome in patients with advanced or metastatic solid tumors or lymphoma. II. Determine the qualitative and quantitative toxic effects of this regimen in this patient population. III. Determine the pharmacokinetics of these drugs in this patient population. IV. Determine the antitumor activity of this regimen in this patient population.

PROTOCOL OUTLINE: This is a dose-escalation study. Patients receive doxorubicin HCl liposome IV over 60 minutes followed by ZD0473 IV over 60 minutes on day 1. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or complete response (CR) may continue treatment until disease progression or until 2 courses after maximum response. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome and ZD0473 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Patients are followed at 4 weeks and 3 months. Patients with PR or CR ongoing continue follow-up every 3 months until relapse.

PROJECTED ACCRUAL: Approximately 24 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced or metastatic solid tumors or lymphoma; Refractory to standard curative therapy OR No curative therapy exists
• Serologically, clinically, and/or radiographically assessable disease
• No newly diagnosed brain metastases; Intracranial disease that is stable for at least 6 months allowed

--Prior/Concurrent Therapy--

• Biologic therapy: At least 5 days since prior immunotherapy
• Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and similar compounds); No more than 3 prior chemotherapy regimens for metastatic disease; No prior anthracycline exposure exceeding 300 mg/m2 doxorubicin; No prior doxorubicin HCl liposome
• Endocrine therapy: At least 5 days since prior hormonal therapy
• Radiotherapy: At least 3 weeks since prior radiotherapy and recovered; No prior radiotherapy to more than 30% of functioning bone marrow
• Surgery: At least 3 weeks since prior major surgery
• Other: No other concurrent experimental drugs; No other concurrent anticancer therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Absolute granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than upper limit of normal (ULN); AST or ALT no greater than 2.0 times ULN; Alkaline phosphatase no greater than 2.0 times ULN
• Renal: Creatinine no greater than ULN; Creatinine clearance at least 60 mL/min
• Cardiovascular: Ejection fraction at least 50%
• Other: No underlying medical condition that would preclude study or that is uncontrolled; No active serious infection; No neurotoxicity or preexisting grade 3 or higher neuropathy; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

David R. Spriggs,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000068603; MSKCC-00044; NCI-G01-1942
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00016172
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08