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

NCT00321581 | Completed Phase 1

• 2 other identifiers: 06015206-C-0152
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Refractory or Recurrent Solid Tumors; Acute Myelogenous Leukemia

Keywords

VEGFR2; Tyrosine Kinase Inhibitor; Antiangiogenesis; Solid Tumors; Childhood Cancer; Solid Tumor; Recurrent Solid Tumor; Treatment Resistant Solid Tumor; Acute Myelogenous Leukemia; AML

Interventions

Cediranib, AZD2171, RECENTIN DRUG

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• AGE: Patients must be greater than 2 years and less than 19 years of age.
• DIAGNOSIS: Solid Tumors (dose escalation component of the trial): Histologically confirmed extracranial malignant solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.
• DISEASE STATUS: Patients with solid tumors must have measurable or evaluable disease.
• \- Patients must be able to swallow tablets intact.
• PRIOR THERAPY: The patient's cancer must have relapsed after or failed to respond to frontline standard therapy and no other standard curative treatment options are available. Standard therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
• Patients must have had their last fraction of radiation therapy:
• at least 4 months prior to study entry for large ports (greater than 50% pelvis, TBI, or craniospinal) for solid tumor patients.
• at least 4 weeks prior to study entry for other radiation in solid tumor patients or for any type of radiation in leukemia patients.
• Patients must have had their last dose of:
• Cytotoxic chemotherapy:
• Patients with solid tumors, the last dose of cytotoxic therapy must be at least 21 days prior to study entry.
• Biological therapy that was administered for the treatment of cancer at least 7 days prior to study entry.
• Immunotherapy (antibody) at least 30 days prior to study entry.
• Any investigational cancer therapy at least 30 days prior to study entry.
• Patients who have received an allogeneic BM or SC transplant must be at least 3 months post-transplant; and patients who have received an autologous BM or SC transplant must be at least 2-months post-transplant.

You may not qualify if:

• Patients with primary brain tumors.
• Patients with a history of congenitally prolonged QTc, or history of arrhythmia (multifocal premature ventricular contractions, bigeminy,trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation, left bundle block) that is symptomatic or requires treatment (except for controlled atrial fibrillation).
• Patients receiving medication for treatment of hypertension or patients with a diastolic blood pressure 5mmHg greater than the 95% for gender and age on 3 measurements using an appropriate size cuff are excluded.
• Patients who have had major surgery within the past 3 months. Patients having minor surgery (e.g., central line placement) within the past 2 weeks.
• Patients with history of arterial or venous thrombosis within the prior 3 months.
• Patients requiring systemic full dose anticoagulation with systemic thrombolytics, heparin, coumadin, or low molecular weight heparin or other anticoagulants for therapy of active thrombosis within the prior 3 months.
• Patients experiencing significant hemorrhage (hemoptysis, melena, or hematemesis) within the past 2 weeks.
• Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal, gastrointestinal or other organ dysfunction, which in the judgment of the principal investigator, protocol chairperson or associate investigator would compromise the patient's ability to tolerate the investigational agent or are likely to interfere with the study procedures or endpoints.
• Patients with active GVHD are excluded.
• Pregnant or breastfeeding females are excluded because Cediranib may be harmful to the developing fetus or nursing child.
• Patients currently receiving other investigational agents.
• Patients previously known to be Hepatitis B, Hepatitis C, or HIV infected because of the unknown interaction of Cediranib with antiviral therapy.
• Patients or first degree relatives of persons that are involved in the planning and conduct of this trial are excluded.
• Patients who have previously received Cediranib.
• Patients who are allergic to Cediranib or its excipients (mannitol, sodium starch glycollate and magnesium stearate).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Childrens Hospital, Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (4)

• Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4-6. doi: 10.1093/jnci/82.1.4. No abstract available.

  PMID: 1688381 BACKGROUND

• Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 1998 Jan 16;279(5349):377-80. doi: 10.1126/science.279.5349.377.

  PMID: 9430587 BACKGROUND

• Konerding MA, Malkusch W, Klapthor B, van Ackern C, Fait E, Hill SA, Parkins C, Chaplin DJ, Presta M, Denekamp J. Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts. Br J Cancer. 1999 May;80(5-6):724-32. doi: 10.1038/sj.bjc.6690416.

  PMID: 10360650 BACKGROUND

• Fox E, Aplenc R, Bagatell R, Chuk MK, Dombi E, Goodspeed W, Goodwin A, Kromplewski M, Jayaprakash N, Marotti M, Brown KH, Wenrich B, Adamson PC, Widemann BC, Balis FM. A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavailable pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors. J Clin Oncol. 2010 Dec 10;28(35):5174-81. doi: 10.1200/JCO.2010.30.9674. Epub 2010 Nov 8.

  PMID: 21060028 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Interventions

cediranib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 3, 2006
• First Posted: May 4, 2006
• Study Start: May 1, 2006
• Study Completion: October 6, 2011
• Last Updated: November 21, 2019

Record last verified: 2012-06-29

Locations

US (1)