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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00004212
First received: January 28, 2000
Last updated: May 15, 2012
Last verified: May 2012
  Purpose

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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Study Start Date: September 1999
Study Completion Date: April 2004
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004212

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105-2794
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
Institute for Drug Development
San Antonio, Texas, United States, 78245-3217
Sponsors and Collaborators
Daiichi Sankyo Inc.
Investigators
Study Chair: Robert L. DeJager, MD, FACP Daiichi Sankyo Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT00004212     History of Changes
Other Study ID Numbers: CDR0000067330, DAIICHI-8951A-PRT013, MSKCC-99071, UTHSC-9895011445, NCI-V99-1573
Study First Received: January 28, 2000
Last Updated: May 15, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
childhood infratentorial ependymoma
childhood supratentorial ependymoma
childhood craniopharyngioma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
childhood central nervous system germ cell tumor
unspecified childhood solid tumor, protocol specific
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
childhood high-grade cerebral astrocytoma
childhood oligodendroglioma
childhood choroid plexus tumor
stage III childhood small noncleaved cell lymphoma
stage III childhood large 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
untreated childhood brain stem glioma
recurrent childhood brain stem glioma
untreated childhood supratentorial primitive neuroectodermal tumor
recurrent childhood supratentorial primitive neuroectodermal tumor
untreated childhood cerebellar astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
untreated childhood medulloblastoma
recurrent childhood medulloblastoma
untreated childhood visual pathway and hypothalamic glioma

Additional relevant MeSH terms:
Lymphoma
Nervous System Neoplasms
Lymphoma, Non-Hodgkin
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Lenograstim
Exatecan
Camptothecin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 23, 2014