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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Cyclophosphamide and Topotecan

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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	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.; Other Names: Cytoxan and Hycamptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Radiographic imaging	Every 2 cycles

Collaborators and Investigators

• Sponsor: Children's Medical Center Dallas
• Collaborators: Metabolic Solutions Inc.; Simmons Cancer Center
• Investigators: Principal Investigator: Daniel C Bowers, MD, UT Southwestern Medical Center of Dallas

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (Estimate): March 5, 2008

Study Record Updates

• Last Update Posted (Estimate): January 28, 2009
• Last Update Submitted That Met QC Criteria: January 27, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: Children; Cyclophosphamide; Topotecan; Phase II; Relapsed solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Cyclophosphamide; Topotecan
• Other Study ID Numbers: 012005004