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
N/A
21 Years
Both
Brain and Central Nervous System Tumors, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Robert L. DeJager, MD, FACP
Investigator Role:
Study Chair
Investigator Affiliation:
Daiichi Sankyo Inc.
Authority:
United States: Federal Government
Study ID:
CDR0000067330
NCT ID:
NCT00004212
Start Date:
September 1999
Completion Date:
April 2004
Related Keywords:
- Brain and Central Nervous System Tumors
- Lymphoma
- Unspecified Childhood Solid Tumor, Protocol Specific
- 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
- recurrent childhood visual pathway and hypothalamic glioma
- newly diagnosed childhood ependymoma
- recurrent childhood ependymoma
- Lymphoma
- Nervous System Neoplasms
- Lymphoma, Non-Hodgkin
- Central Nervous System Neoplasms
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| Institute for Drug Development | San Antonio, Texas 78245-3217 |
| Children's Medical Center of Dallas | Dallas, Texas 75235 |
