A Pharmacokinetic and Phase II Study of Oral Cyclophosphamide and Topotecan in Children With Recurrent Solid Tumors - Full Text View

Sponsors and Collaborators:	Children's Medical Center Dallas Metabolic Solutions Inc. Simmons Cancer Center
Information provided by:	Children's Medical Center Dallas
ClinicalTrials.gov Identifier:	NCT00628732

Purpose

The purposes of this study include:

Determination of the change in clearance of topotecan and topotecan lactone between day 1 and day 14 for patients receiving treatment with p.o. topotecan and p.o. cyclophosphamide x 14 days.
Determination of the correlation between the activity of CYP3A4, as measured by the 14C- Erythromycin Breath Test (ERMBT), and topotecan/topotecan lactone clearance for patients receiving treatment with p.o. topotecan and p.o. cyclophosphamide x 14 days.
Determination of the response rate to oral cyclophosphamide and oral topotecan in recurrent and/or refractory pediatric solid tumors.
Obtain additional safety data for the chemotherapy regimen, p.o. topotecan and p.o. cyclophosphamide x 14 days.
Report the frequency of severe toxicities associated with the level of CYP3A4 activity, as measured by the ERMBT, for patients receiving treatment with p.o. topotecan and p.o. cyclophosphamide x 14 days.

Condition	Intervention	Phase
Solid Tumors	Drug: Cyclophosphamide and Topotecan	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Topotecan hydrochloride Topotecan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pharmacokinetic and Phase II Study of Oral Cyclophosphamide and Oral Topotecan in Children With Recurrent and or Refractory Solid Tumors

Further study details as provided by Children's Medical Center Dallas:

Primary Outcome Measures:

Radiographic imaging [ Time Frame: Every 2 cycles ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	January 2005
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Cyclophosphamide and Topotecan Two courses of cyclophosphamide at 50 mg/m2/dose and topotecan 0.8 mg/m2/dose by mouth every morning for 14 days each.

Detailed Description:

Upon obtaining informed consent, patients will begin two courses of oral cyclophosphamide and topotecan x 14 days. During the first of two courses, patients will perform the 14C-Erythromycin Breath Test and have topotecan pharmacokinetics performed on day 1 and 14. The subjects will also have various medical tests and procedures performed that are part of regular cancer care which include: Medical history and physical examination to be done weekly, blood tests to be done weekly, heart and kidney function tests, various scans to be done after two courses of treatment, and a pregnancy test for females of childbearing age to be done prior to starting treatment.

Patients may continue to receive additional courses of oral cyclophosphamide and topotecan provided that they do not experience tumor progression or intolerable side effects.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must be less than 22 years of age inclusive
Tumor histologies: medulloblastoma/PNET, neuroblastoma, sarcomas, and other pediatric solid tumors for which there is no known effective therapy.
Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria.
Patients must have a performance status of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients <= 16 years of age.
Patients must have a life expectancy of >= 8 weeks.
Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Patients must not be taking the following medications: growth factors, steroids, and CYP3A4 inducers or inhibitors.
Patients must have adequate bone marrow, renal, liver function, pulmonary, or central nervous system function.
Must be able and willing to participate in all study procedures, including the ERMBT and pharmacokinetic studies.
All patients and/or their parents or legal guardians must sign a written informed consent. (11) All institutional, FDA, and NCI requirements for human studies must be met.

Exclusion Criteria:

Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Patients with an uncontrolled infection.
Allergy to erythromycin
Patients who have previously received either cyclophosphamide or topotecan are eligible for this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628732

Contacts

Contact: Jennifer L Evans, B.A., B.S.	214.456.8138	jennifer.evans@childrens.com
Contact: Tanja M. Hoffman, RN, MSN	214.456.2726	tanja.hoffman@childrens.com

Locations

United States, Texas
Children's Medical Center Dallas	Recruiting
Dallas, Texas, United States, 75235

Sponsors and Collaborators

Children's Medical Center Dallas

Metabolic Solutions Inc.

Simmons Cancer Center

Investigators

Principal Investigator:

Daniel C Bowers, MD

UT Southwestern Medical Center of Dallas

More Information

Responsible Party:	UT Southwestern Medical Center of Dallas ( Daniel C. Bowers M.D./ Associate Professor of Pediatrics )
Study ID Numbers:	012005004
Study First Received:	February 25, 2008
Last Updated:	February 25, 2008
ClinicalTrials.gov Identifier:	NCT00628732
Health Authority:	United States: Institutional Review Board

Keywords provided by Children's Medical Center Dallas:

Cyclophosphamide
Topotecan
Phase II
Children
Relapesed solid tumors

Study placed in the following topic categories:

Cyclophosphamide
Topotecan
Recurrence

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Myeloablative Agonists

Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009