DX-8951f in Treating Children With Advanced Solid Tumors or Lymphomas

Daiichi Sankyo

Status and phase: Completed; Phase 1

Conditions: Brain and Central Nervous System Tumors; Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Biological: filgrastim; Drug: exatecan mesylate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00004212

CDR0000067330

UTHSC-9895011445

MSKCC-99071

NCI-V99-1573

DAIICHI-8951A-PRT013

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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