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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004212
• Other study ID #: CDR0000067330
• Secondary ID: DAIICHI-8951A-PR
• Status: Completed
• Phase: Phase 1
• First received: January 28, 2000
• Last updated: May 15, 2012
• Start date: September 1999
• Est. completion date: April 2004

Study information

• Verified date: May 2012
• Source: Daiichi Sankyo Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: April 2004
• Est. primary completion date: April 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Lymphoma
• Neoplasms
• Nervous System Neoplasms
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Biological:
• filgrastim

Drug:
• exatecan mesylate

Locations

Country	Name	City	State
United States	Children's Medical Center of Dallas	Dallas	Texas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Institute for Drug Development	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Inc.

Country where clinical trial is conducted

United States,