Clinical trial NCT00187031: A Phase II Study of Topotecan in Children With Recurrent Wilms Tumor
Official title: A Phase II Study of Topotecan in Children With Recurrent Wilms Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Wilms Tumor
Keywords: Wilms Tumor
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: National Institutes of Health (NIH)
First posted: 2005-09-16
Enrollment: 37
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In spite of the overall success of treating Wilms tumor, certain patients still have poor clinical outcomes. The sub-optimal outcomes for patients with anaplastic histology and recurrent Wilms tumor warrant the identification of new therapeutic agents. The objective of this trial is to estimate the response rate to two cycles of intravenous topotecan in children with recurrent Wilms tumor of favorable histology that is refractory to standard curative therapy.

Detailed description: Topotecan administered intravenously over 30 minutes daily for 5 consecutive days for 2 consecutive weeks, with a two-day rest given in between the five-day treatment blocks. The topotecan dose started at 1.8 mg/m2/dosage and adjusted to attain a target systemic exposure of 80 plus or minus 10 ng-hr/ml.each cycle consists of 28 days and subsequent cycles can be administered upon hematological recovery. Patients with a CR, PR, or SD, can continue to receive up to a total of six cycles. Patients with PD are removed from the study.

Secondary Objectives include:

* To describe the anti-tumor activity of topotecan in children with recurrent Wilms tumor of anaplastic histology.
* To assess the relation between CYP3A4/5 genotype and the pharmacokinetics and pharmacodynamics of topotecan.
* To assess the relation between ABCG2 genotype and the pharmacokinetics and pharmacodynamics of topotecan.

Eligibility criteria: Inclusion Criteria:

* Favorable histology Wilms tumor that has recurred or progressed after primary treatment and at least one standard salvage treatment regimen OR anaplastic histology Wilms tumor that has recurred or progressed after primary treatment
* Age\< 21 years of age at the time of study entry
* Adequate bone marrow function
* Adequate liver function
* Adequate renal function
* Adequate performance status

Exclusion Criteria:

* Subject is pregnant
* Subject is lactating
* Renal tumors other than Wilms tumors

Primary outcomes:
measure: Response rate (complete and partial response as per RECIST criteria).
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare
state: Georgia
city: Boston
country: United States
facility: Dana Farber
state: Massachusetts
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Toronto
country: Canada
facility: Hospital of Sick Children
state: Ontario
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Monika Metzger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Metzger ML, Stewart CF, Freeman BB 3rd, Billups CA, Hoffer FA, Wu J, Coppes MJ, Grant R, Chintagumpala M, Mullen EA, Alvarado C, Daw NC, Dome JS. Topotecan is active against Wilms' tumor: results of a multi-institutional phase II study. J Clin Oncol. 2007 Jul 20;25(21):3130-6. doi: 10.1200/JCO.2007.10.9298.