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

NCT ID: NCT00004212

Last Updated: 2012-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-09-30
• Study Completion Date: 2004-04-30

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.

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.

Conditions

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

Study Design

• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

exatecan mesylate

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert L. DeJager, MD, FACP

Role: STUDY_CHAIR

Daiichi Sankyo

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Children's Medical Center of Dallas

Dallas, Texas, United States

Institute for Drug Development

San Antonio, Texas, United States

Countries

United States

Other Identifiers

DAIICHI-8951A-PRT013

Identifier Type: -

Identifier Source: secondary_id

MSKCC-99071

Identifier Type: -

Identifier Source: secondary_id

UTHSC-9895011445

Identifier Type: -

Identifier Source: secondary_id

NCI-V99-1573

Identifier Type: -

Identifier Source: secondary_id

CDR0000067330

Identifier Type: -

Identifier Source: org_study_id