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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


Phase 1
N/A
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

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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 CenterNew York, New York  10021
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Institute for Drug DevelopmentSan Antonio, Texas  78245-3217
Children's Medical Center of DallasDallas, Texas  75235