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

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00004212

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Lymphoma Unspecified Childhood Solid Tumor, Protocol Specific	Biological: filgrastim Drug: exatecan mesylate	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Dose Escalation Study of Intravenous DX-8951f Administered Daily for Five Days Every Three Weeks to Pediatric Patients With Advanced Solid Tumors and Lymphomas

Study Start Date :

Sep 1, 1999

Actual Primary Completion Date :

Apr 1, 2004

Actual Study Completion Date :

Apr 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
2	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
3	Children's Medical Center of Dallas	Dallas	Texas	United States	75235
4	Institute for Drug Development	San Antonio	Texas	United States	78245-3217