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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Brain and Central Nervous System Tumors
• Intervention / Treatment: Biological: filgrastim; Drug: exatecan mesylate

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 Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 1999
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: January 28, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 16, 2012
• Last Update Submitted That Met QC Criteria: May 15, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific; untreated childhood brain stem glioma; childhood high-grade cerebral astrocytoma; stage III childhood small noncleaved cell lymphoma; stage IV childhood small noncleaved cell lymphoma; stage IV childhood large cell lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; recurrent/refractory childhood Hodgkin lymphoma; stage III childhood large cell lymphoma; stage III childhood lymphoblastic lymphoma; stage IV childhood lymphoblastic lymphoma; untreated childhood medulloblastoma; untreated childhood cerebellar astrocytoma; childhood infratentorial ependymoma; newly diagnosed childhood ependymoma; stage IV childhood Hodgkin lymphoma; recurrent childhood lymphoblastic lymphoma; stage III childhood Hodgkin lymphoma; childhood supratentorial ependymoma; childhood oligodendroglioma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood brain stem glioma; recurrent childhood medulloblastoma; recurrent childhood visual pathway and hypothalamic glioma; childhood craniopharyngioma; childhood central nervous system germ cell tumor; childhood choroid plexus tumor; untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood visual pathway and hypothalamic glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Neoplasms; Lymphoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Exatecan
• Other Study ID Numbers: CDR0000067330; DAIICHI-8951A-PRT013; MSKCC-99071; UTHSC-9895011445; NCI-V99-1573