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

• ClinicalTrials.gov Identifier: NCT00628732
• Recruitment Status: Completed
• First Posted: March 5, 2008
• Last Update Posted: January 28, 2009
• Sponsor: Children's Medical Center Dallas
• Collaborators: Metabolic Solutions Inc.; Simmons Cancer Center
• Information provided by: Children's Medical Center Dallas

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Drug: Cyclophosphamide and Topotecan	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pharmacokinetic and Phase II Study of Oral Cyclophosphamide and Oral Topotecan in Children With Recurrent and or Refractory Solid Tumors
• Study Start Date: January 2005
• Actual Primary Completion Date: February 2007
• Actual Study Completion Date: February 2007

Arms and Interventions

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 Name: Cytoxan and Hycamptin

Outcome Measures

Primary Outcome Measures :

1. Radiographic imaging [ Time Frame: Every 2 cycles ]

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Texas

Children's Medical Center Dallas

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: Daniel C. Bowers M.D./ Associate Professor of Pediatrics, UT Southwestern Medical Center of Dallas
• ClinicalTrials.gov Identifier: NCT00628732
• Other Study ID Numbers: 012005004
• First Posted: March 5, 2008
• Last Update Posted: January 28, 2009
• Last Verified: January 2009

Keywords provided by Children's Medical Center Dallas:

Cyclophosphamide; Topotecan; Phase II; Children; Relapsed solid tumors

Additional relevant MeSH terms:

Neoplasms; Cyclophosphamide; Topotecan; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors