A Pharmacokinetic Study of Oral Cyclophosphamide and Topotecan in Children With Recurrent Solid Tumors

Solid Tumors Clinical Trial

Official title:

A Pharmacokinetic and Phase II Study of Oral Cyclophosphamide and Oral Topotecan in Children With Recurrent and or Refractory Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00628732
• Other study ID #: 012005004
• Status: Completed
• Phase: Phase 2
• First received: February 25, 2008
• Last updated: January 27, 2009
• Start date: January 2005
• Est. completion date: February 2007

Study information

• Verified date: January 2009
• Source: Children's Medical Center Dallas
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

1. Patients must be less than 22 years of age inclusive

2. Tumor histologies: medulloblastoma/PNET, neuroblastoma, sarcomas, and other pediatric solid tumors for which there is no known effective therapy.

3. Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria.

4. 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.

5. Patients must have a life expectancy of >= 8 weeks.

6. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

7. Patients must not be taking the following medications: growth factors, steroids, and CYP3A4 inducers or inhibitors.

8. Patients must have adequate bone marrow, renal, liver function, pulmonary, or central nervous system function.

9. Must be able and willing to participate in all study procedures, including the ERMBT and pharmacokinetic studies.

10. 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:

1. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

2. Patients with an uncontrolled infection.

3. Allergy to erythromycin

4. Patients who have previously received either cyclophosphamide or topotecan are eligible for this study.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

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.

Locations

Country	Name	City	State
United States	Children's Medical Center Dallas	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Children's Medical Center Dallas	Metabolic Solutions Inc., Simmons Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic imaging		Every 2 cycles	Yes