Topotecan Hydrochloride in Treating Children With Meningeal Cancer That Has Not Responded to Previous Treatment

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005811
• Other study ID #: NCI-2012-01848
• Secondary ID: P9962U10CA098543
• Status: Completed
• Phase: Phase 2
• First received: June 2, 2000
• Last updated: February 20, 2013
• Start date: April 2000
• Est. completion date: February 2009

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well topotecan hydrochloride works in treating children with meningeal cancer that has not responded to previous treatment

Description:

PRIMARY OBJECTIVES:

I. Determine the therapeutic activity of intrathecal topotecan, in terms of response rate and time to central nervous system (CNS) progression, in pediatric patients with recurrent or refractory neoplastic meningitis.

II. Determine the safety and toxicity of this regimen in these patients. III. Evaluate the concentration of matrix metalloproteinases (MMPs) in the cerebrospinal fluid (CSF) of these patients.

OUTLINE: Patients are stratified according to disease type (acute lymphoblastic leukemia vs. other leukemia/lymphoma vs medulloblastoma vs other solid tumors). (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)

INDUCTION: Patients receive topotecan hydrochloride intrathecally (IT) over 5 minutes twice weekly for 6 weeks.

CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan hydrochloride IT over 5 minutes weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning 2 weeks after completion of consolidation, patients receive topotecan hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1.

After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 14-77 patients will be accrued for this study.

Other known NCT identifiers

• NCT00013676

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: February 2009
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

Inclusion Criteria:

• Histologically proven refractory leukemia, lymphoma, or other solid tumor thathas overt meningeal involvement (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)

• Definition of meningeal disease:

• Leukemia/lymphoma (including acute lymphoblastic leukemia)

• CSF cell count greater than 5/mm^3 AND evidence of blast cells oncytospin preparation or by cytology

• Refractory to conventional therapy, including radiotherapy (i.e., in second or greater relapse)

• No concurrent bone marrow relapse

• Solid tumors (including medulloblastoma)

• Presence of tumor cells on cytospin preparation or cytology OR presence ofmeningeal disease on MRI scans

• No clinical evidence of obstructive hydrocephalus or compartmentalization ofCSF flow as documented by radioisotope indium In 111 or technetium Tc 99 DTPAflow study

• If CSF flow block is demonstrated, focal radiotherapy must be administered tosite of block to restore flow and a repeat CSF flow study must show clearing of blockage

• No ventriculoperitoneal or ventriculoatrial shunt unless:

• Patient is shunt independent and there is evidence that the shunt is nonfunctional

• CSF flow study demonstrates normal flow

• No impending cord compression, CNS involvement requiring local radiotherapy(e.g., optic nerve), or isolated bulky ventricular or leptomeningeal basedlesions

• Performance status - Lansky 50-100% (age 10 and under)

• Performance status - Karnofsky 50-100% (over age 10)

• At least 8 weeks

• Platelet count greater than 40,000/mm^3 (transfusions allowed)

• Bilirubin less than 2.0 mg/dL

• SGPT less than 5 times normal

• Creatinine less than 1.5 mg/dL

• Electrolytes, calcium, and phosphorus normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No significant illness (e.g., uncontrolled infection, except HIV [i.e., AIDS-related lymphomatous meningitis])

• Prior immunotherapy allowed and recovered

• At least 3 weeks since systemic CNS directed chemotherapy (6 weeks for nitrosoureas) and recovered

• At least 1 week since prior intrathecal (IT) chemotherapy (2 weeks for cytarabine [liposomal])

• No prior IT chemotherapy on days -14 to -7 before study entry unless evidence of disease progression (e.g., increasing WBC and percentage blasts in patients with leukemia/lymphoma or increased leptomeningeal enhancements in patients with solid tumors) (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)

• Concurrent chemotherapy to control systemic disease or bulk CNS disease allowed if the systemic chemotherapy is not a phase I study agent that significantly penetrates the CSF (e.g., high-dose systemic methotrexate [greater than 1 g/m^2], thiotepa, high-dose cytarabine, temozolomide, IV mercaptopurine, nitrosourea, or topotecan) or an agent known to have serious unpredictable CNS side effects

• Concurrent dexamethasone or prednisone allowed if part of a systemic chemotherapy regimen

• See Disease Characteristics

• At least 8 weeks since prior cranial irradiation and recovered

• No concurrent whole brain or craniospinal irradiation

• At least 7 days since prior investigational drug

• Time period should be extended if patient has received any investigational agent that is known to have delayed toxic effects after 7 days or a prolonged half-life

• No other concurrent investigational agents

• No concurrent therapy (IT or systemic) for leptomeningeal disease

• No other concurrent systemic agents that significantly penetrate the blood-brain barrier

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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
• Childhood Diffuse Large Cell Lymphoma
• Childhood Immunoblastic Large Cell Lymphoma
• HIV-associated Hodgkin Lymphoma
• Hodgkin Disease
• Leptomeningeal Metastases
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Non-Hodgkin
• Medulloblastoma
• Meningeal Carcinomatosis
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Recurrent Childhood Large Cell Lymphoma
• Recurrent Childhood Lymphoblastic Lymphoma
• Recurrent Childhood Medulloblastoma
• Recurrent Childhood Small Noncleaved Cell Lymphoma
• Recurrent/Refractory Childhood Hodgkin Lymphoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• topotecan hydrochloride
Given IT

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Children's Oncology Group	Arcadia	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For the leukemia and lymphoma patients, an objective response rate, defined to be the proportion of Complete Responses of less than 0.10		Up to 54 months	No
Primary	For the patients with solid tumors, a proportion of patients who do not experience an event, defined to be death, progressive disease, relapse, or second malignancy of less than 0.3		Up to 54 months	No
Primary	Safety and toxicity		Up to 54 months	Yes
Primary	Concentration of matrix metalloproteinases in the CSF		Up to 54 months	No