Clinical trial NCT00004212: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Lymphoma
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2003-01-27
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: San Antonio
country: United States
facility: Institute for Drug Development
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Robert L. DeJager, MD, FACP
role: STUDY_CHAIR
References: