AZD2171 to Treat Children and Adolescents With Solid Tumors or Acute Myelogenous Leukemia

Acute Myelogenous Leukemia Clinical Trial

Official title: Phase I Trial of CEDIRANIB (AZD2171), an Orally Bioavailable Antiangiogenic Agent, in Children and Adolescents With Refractory or Recurrent Solid Tumors

Status Completed

Clinical Trial Summary

Background:

• AZD2171 is an experimental drug that may slow the growth of cancers by blocking angiogenesis (formation of new blood vessels).

• Cancer growth is dependent on angiogenesis for nutrition.

• Inhibiting angiogenesis is a new approach to cancer therapy.

Objectives:

• To determine the side effects of AZD2171 in children and adolescents with cancer.

• To determine the highest dose of AZD2171 that can safely be given to children and adolescents with cancer.

• To study how the body handles AZD2171.

• To determine the effects of AZD2171 on various factors related to angiogenesis.

• To determine if AZD2171 can inhibit cancer growth in children and adolescents.

Eligibility:

-Children and adolescents 2-18 years of age with treatment-resistant solid tumor cancers or acute myelogenous leukemia.

Design:

• About 40 patients may be included in the study.

• AZD2171 is given by mouth in treatment cycles of once a day for 28 days. Treatment may continue unless the cancer worsens or unacceptable side effects develop.

• Patients have periodic physical examinations, blood and urine tests and imaging tests (CT, X-rays, MRI) to evaluate disease throughout the course of treatment. Additional blood tests are done to study how the body handles AZD2171, to look for proteins that stimulate angiogenesis, to determine if certain blood vessel cells are affected by AZD2171, and for other research purposes.

• Biopsy tissue (when available) is examined for the receptor for new blood vessel formation.

Clinical Trial Description

Background:

• Cediranib is a potent orally bioavailable inhibitor of VEGFR1, VEGFR2, VEGFR3 tyrosine kinase activity, but also inhibits c-kit and PDGFR-Beta in vitro.

• Phase I trials of Cediranib are ongoing in adults and the drug is well tolerated at doses up to 45 mg/d. The toxicity profile includes hypertension, hypoglycemia, elevated LFTs, fatigue, dysphonia, diarrhea, nausea and vomiting.

Objectives:

• To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of orally administered Cediranib on a daily for 28 consecutive days schedule in children and adolescents with refractory childhood solid tumors.

• To define the toxicity spectrum of oral Cediranib in children and adolescents.

• To assess the pharmacokinetics and pharmacodynamics of oral Cediranib in children and adolescents.

• Assess growth plate volume in the right knee using non-contrast MRI scans prior to and during administration of cediranib.

Eligibility:

-Children and adolescents (greater than 2 yrs and less than 19 years of age) with histologically confirmed relapsed or refractory extracranial solid tumors that are measurable or evaluable.

Design:

• Cediranib will be administered orally, daily. Treatment cycles are 28 days with no break in treatment between cycles. The starting dose level is 12 mg/m(2)/d with escalations to 17, 25, 35, and 50 mg/ m(2)/d, due to dose limiting toxicity in the initial 2 subjects enrolled at 12 mg/m(2)/d the protocol was amended to restart dose escalation at 8 mg/m(2)/d.

• Detailed pharmacokinetic and pharmacodynamic studies will be performed during the first 28 day treatment cycle.

• The trial follows a standard phase I design with 3 to 6 patients per dose level and standard definitions of MTD and DLT. Up to 28 patients will be entered on this trial. ;

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasms
• Refractory or Recurrent Solid Tumors

• NCT number: NCT00321581
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: May 1, 2006
• Completion date: October 6, 2011