RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of DX-8951f in treating children who have advanced solid tumors or lymphomas that have not responded to previous therapy.

Condition	Treatment or Intervention	Phase
childhood Hodgkin's lymphoma childhood brain tumor childhood non-Hodgkin's lymphoma childhood solid tumor	Drug: exatecan mesylate  Drug: filgrastim  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of exatecan mesylate (DX-8951f) with and without filgrastim (G-CSF) in pediatric patients with advanced solid tumors or lymphomas.
• Determine the toxic effects, including dose-limiting toxicity, of exatecan mesylate in these patients.
• Determine the pharmacokinetics of exatecan mesylate in these patients.
• Determine the recommended dose of exatecan mesylate for phase II study.
• Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of exatecan mesylate (DX-8951f). Patients are stratified according to prior treatment (minimally treated vs heavily treated).

Patients receive exatecan mesylate IV over 30 minutes daily for 5 days. Patients in dose levels 5 and above also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing for at least 7 days or until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of exatecan mesylate with and without G-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumors, including brain tumors and lymphomas, that have failed standard therapy (surgery, radiotherapy, endocrine therapy, or chemotherapy) or for which no standard therapy exists
• Histology requirement waived for brain stem gliomas

PATIENT CHARACTERISTICS: Age:

• 21 and under at diagnosis

Performance status:

• ECOG 0-2

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 750/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 8.5 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT or SGPT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases)

Renal:

• Creatinine no greater than 1.5 times ULN OR
• GFR at least 70 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• No history of severe or life-threatening hypersensitivity to camptothecin analogs
• HIV negative
• No other concurrent severe or uncontrolled medical illness
• No systemic infection

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Recovered from prior immunotherapy

Chemotherapy:

• See Disease Characteristics
• Recovered from prior chemotherapy

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior extensive radiotherapy involving cranial, whole pelvic, or at least 25% of bone marrow reserve
• Recovered from prior radiotherapy
• Concurrent localized radiotherapy for pain allowed

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• No other concurrent antitumor therapy
• No concurrent drugs that induce or inhibit CYP3A enzyme

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
Texas
      Children's Medical Center of Dallas, Dallas,  Texas,  75235,  United States
      Institute for Drug Development, San Antonio,  Texas,  78245-3217,  United States

Study chairs or principal investigators

Robert L. DeJager, MD, FACP,  Study Chair,  Daiichi Pharmaceuticals   

Study ID Numbers:  CDR0000067330; DAIICHI-8951A-PRT013; MSKCC-99071; UTHSC-9895011445; NCI-V99-1573
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004212
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08