Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors

NCT ID: NCT00112619

Last Updated: 2011-06-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of topotecan when given by intraventricular infusion in treating young patients with neoplastic meningitis due to leukemia, lymphoma, or solid tumors.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of intraventricular topotecan in young patients with neoplastic meningitis secondary to leukemia, lymphoma, or solid tumors.
• Determine the toxic effects and dose-limiting toxicity of this drug in these patients.
• Determine whether the MTD of this drug is also the pharmacokinetic optimal dose, defined by the topotecan lactone concentration in the cerebral spinal fluid (CSF), in these patients.

Secondary

• Determine, preliminarily, the antitumor activity of this drug in these patients.
• Determine the pharmacokinetics of this drug in the CSF of these patients.
• Correlate observed effects of post-treatment central review imaging (if feasible) with response to this drug in these patients.

OUTLINE: This is a non-randomized, dose-escalation, multicenter study.

• Induction therapy (weeks 1-4): Patients receive topotecan intraventricularly* over 5 minutes on days 1-5 in weeks 1 and 3. Patients then proceed to consolidation therapy in week 5.

NOTE: *Patients who are willing, receive 1 intralumbar (instead of intraventricular) dose of topotecan on day 1 of week 3 only.

• Consolidation therapy (weeks 5-10): Patients receive topotecan intraventricularly on days 1-5 in weeks 5 and 8. Patients then proceed to maintenance therapy in week 11.
• Maintenance therapy (weeks 11-54): Patients receive topotecan intraventricularly on days 1-5 in weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51.

Cohorts of 3-6 patients receive escalating doses of intraventricular topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, the cohort is expanded to 25 patients and the MTD is declared the pharmacokinetic optimal dose provided 23 of 25 patients treated at the MTD achieve the target pharmacokinetic parameter.

PROJECTED ACCRUAL: A total of 28-49 patients will be accrued for this study within 9-24 months.

Conditions

Brain and Central Nervous System Tumors; Carcinoma of Unknown Primary; Leukemia; Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

AIDS-related diffuse large cell lymphoma; AIDS-related diffuse mixed cell lymphoma; AIDS-related diffuse small cleaved cell lymphoma; AIDS-related immunoblastic large cell lymphoma; AIDS-related lymphoblastic lymphoma; AIDS-related peripheral/systemic lymphoma; AIDS-related primary CNS lymphoma; AIDS-related small noncleaved cell lymphoma; HIV-associated Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma; stage IV childhood large cell lymphoma; stage IV childhood lymphoblastic lymphoma; stage IV childhood small noncleaved cell lymphoma; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; unspecified childhood solid tumor, protocol specific; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebral astrocytoma; childhood choroid plexus tumor; childhood craniopharyngioma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; childhood oligodendroglioma; recurrent childhood supratentorial primitive neuroectodermal tumor; leptomeningeal metastases; recurrent carcinoma of unknown primary; childhood central nervous system germ cell tumor; childhood chronic myelogenous leukemia; juvenile myelomonocytic leukemia; recurrent/refractory childhood Hodgkin lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; recurrent childhood visual pathway and hypothalamic glioma; childhood atypical teratoid/rhabdoid tumor; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; relapsing chronic myelogenous leukemia; recurrent childhood pineoblastoma; recurrent childhood subependymal giant cell astrocytoma; meningeal leukemia; secondary central nervous system Hodgkin lymphoma; secondary central nervous system non-Hodgkin lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

topotecan hydrochloride

Participants receive intraventricular topotecan, .2 mg, administered via an indwelling ventricular reservoir daily for 5 consecutive days during weeks 1 and 3 of the first four weeks of therapy (induction), during weeks 5 and 8 of the next 6 weeks of therapy (consolidation), and during weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51 (maintenance therapy).

Intervention Type: DRUG

Other Intervention Names

Hycamptin

Eligibility Criteria

Inclusion Criteria

• No other significant uncontrolled systemic medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior biologic therapy or immunotherapy

Chemotherapy

• Recovered from prior chemotherapy
• At least 1 week since prior intra-colony stimulating factory (CSF) chemotherapy (2 weeks for liposomal cytarabine)
• At least 3 weeks since prior systemic chemotherapy for leptomeningeal disease
• Concurrent systemic chemotherapy to control systemic disease or bulk CNS disease allowed provided the systemic chemotherapy is not an investigational agent OR any of the following:

• High-dose (> 1 g/m^2) methotrexate
• High-dose (> 1 g/m^2) cytarabine
• Fluorouracil
• Capecitabine
• Thiotepa
• Nitrosoureas
• Topotecan

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 8 weeks since prior craniospinal radiotherapy and recovered
• No concurrent CNS radiotherapy

• Concurrent radiotherapy to extra-CNS sites (e.g., painful bone metastases not in the craniospinal axis) allowed

Surgery

• Not specified

Other

• More than 2 weeks since prior and no other concurrent investigational agents
• No other concurrent intra-CSF or systemic therapy for leptomeningeal disease

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Pediatric Brain Tumor Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Pediatric Brain Tumor Consortium

Principal Investigators

Susan M. Blaney, MD

Role: STUDY_CHAIR

Baylor College of Medicine

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Dan L. Duncan Cancer Center at Baylor College of Medicine

Houston, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Countries

United States

Other Identifiers

U01CA081457

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PBTC-019

Identifier Type: -

Identifier Source: secondary_id

CDR0000430504

Identifier Type: -

Identifier Source: org_study_id