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

This study has been completed.
Study NCT00004212.   Last updated on July 23, 2008.   Information provided by National Cancer Institute (NCI)

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Descriptive Information Fields
Brief Title  DX-8951f in Treating Children With Advanced Solid Tumors or Lymphomas
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
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.

Study Phase Phase I
Study Type  Interventional
Study Design  Treatment
Primary Outcome Measure 
Secondary Outcome Measure 
Condition  Brain and Central Nervous System Tumors
Lymphoma
Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  Drug: exatecan mesylate
Drug: filgrastim
MEDLINE PMIDs
Links Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Completed
Enrollment 
Start Date  September 1999
Completion Date
Eligibility 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
Gender Both
Ages up to 21 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00004212
Organization ID CDR0000067330
Secondary IDs †† DAIICHI-8951A-PRT013, MSKCC-99071, UTHSC-9895011445, NCI-V99-1573
Study Sponsor  Daiichi Sankyo Inc.
Collaborators ††
Investigators 
Study Chair:     Robert L. DeJager, MD, FACP     Daiichi Sankyo Inc.    
Information Provided By National Cancer Institute (NCI)
Verification Date April 2004
First Received Date  January 28, 2000
Last Updated Date July 23, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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