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Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00942877
First received: July 18, 2009
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

Background:

  • Alveolar soft part sarcoma is a type of cancer that develops in tissues that connect, support, or surround other organs in the body. It relies heavily on new blood vessels to grow and spread through the body. There is no effective systemic treatment for patients with alveolar soft part sarcoma.
  • The drug AZD2171 (cediranib) is an experimental drug, not yet approved by the Food and Drug Administration. The drug blocks the creation of new blood vessels. The drug has had initial clinical trials, and researchers are interested in determining whether cediranib is effective in inhibiting tumor growth in individuals who have alveolar soft part sarcoma.

Objectives:

- To find out whether AZD2171 works in patients who have alveolar soft part sarcoma.

Eligibility:

- Individuals 18 years of age and older who have been diagnosed with alveolar soft part sarcoma.

Design:

  • After an initial screening visit, patients will take AZD2171 by mouth once a day, every day for the duration of the study. The treatment will be given in 28-day cycles.
  • Patients will keep a study diary to record the doses taken, any missed doses, and any side effects.
  • Patients will have the following tests and procedures during the treatment period: clinic visit with physical examination every 2 weeks, regular blood pressure monitoring, blood and urine tests, heart function tests, imagining scans to evaluate tumor size and response to the treatment, and possible tumor biopsy.

Condition Intervention Phase
Sarcoma, Alveolar Soft Part
Drug: AZD2171
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine if pediatric patients with ASPS will experience at least a minimal response rate when treated with AZD2171 [ Time Frame: 2 cycles ] [ Designated as safety issue: No ]

Estimated Enrollment: 73
Study Start Date: July 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Pediatric patients (& lt; 16 years old) will be treated with 12 mg/m2/day once a day for 28 days (28-day cycles).
Drug: AZD2171
Cediranib (AZD2171), a VEGF/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with ASPS.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients must have histologically confirmed alveolar soft part sarcoma. Pathology should be confirmed at the Laboratory of Pathology, National Institutes of Health.

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 millimeters with conventional techniques or as greater than or equal to 10 millimeters with spiral CT scan.

Patients must have metastatic alveolar soft part sarcoma that is not curable by surgery.

Patients who have surgically resectable tumors with metastasis will be considered on a case by- case basis.

Any prior therapy must have been completed greater than or equal to 4 weeks prior to enrollment on protocol and the participant must have recovered to eligibility levels from prior toxicity. Patients should be at least 6 weeks out from nitrosoureas and mitomycin C. Prior radiation should have been completed greater than or equal to 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a sub-therapeutic dose of drug is administered) at the PI s discretion, and should haverecovered to eligibility levels from any toxicities.

Any degree of prior treatment is allowed, including other anti-angiogenic treatments (e.g., VEGFR2 inhibitors or bevacizumab). Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery.

BSA greater than or equal to 0.63 square meter.

ECOG performance status less than or equal to 2 for adults, Karnofsky performance status greater than or equal to 50% for pediatric patients greater than 10 years of age, and Lansky performance status greater than or equal to 50 for pediatric patients less than or equal to 10 years of age.

Life expectancy of greater than 8 weeks.

Patients must have normal organ and marrow function as defined below:

  • absolute neutrophil count greater than or equal to 1,500/microliter
  • platelets greater than or equal to 100,000/microliter
  • total bilirubin less than 1.5 times institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
  • creatinine within normal limits based on age as follows:

Age (Years) Maximum Serum Creatinine (milligrams per deciliter)

less than or equal to 5 0.8

5 less than age less than or equal to 10 1.0

10 less than age less than or equal to 15 1.2

greater than 15 1.5

OR

creatinine clearance greater than or equal to 60 milliter/min for adults or greater than or equal to 60 milliter/min/1.73m2 for children with creatinine levels above institutional upper

limit of normal.

QTc must be less than 500 msec.

Pediatric patients: Normal left ventricular function with ejection fraction greater than 55% or shortening fraction greater than or equal to 7%.

At present, the potential of AZD2171 for clinically significant drug interactions involving the CYP isozymes is unknown. However, studies of the agent in rats indicated possible suppression of CYP1A that may be of biological significance. A list of drugs that may interact with the cytochrome P450 system is included.

Eligibility of patients receiving any medications or substances known

to affect or with the potential to affect the activity of PK of AZD2171 will be determined following review of their case by the Principal Investigator. Efforts should be made to switch patients with brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications one week prior to starting therapy.

AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling. For this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Ability to understand and the willingness to sign a written informed consent document.

Patients should not be receiving any other investigational agents.

Prior therapy with anti-angiogenic agents is permitted.

EXCLUSION CRITERIA:

Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to: active or uncontrolled infection, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.

Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, ibuprofen, pentamidine).

Patients who are unable to swallow tablets.

Mean QTc greater than 500 msec (with Bazett s correction) in screening electrocardiogram or history of familial long QT syndrome.

Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart.

Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171.

HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with AZD2171.

Hypertension not controlled by medical therapy (hypertension defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management).

Adult patients with hypertension not controlled by medical therapy (hypertension defined as systolic blood pressure greater than 150 millimeters of mercury or diastolic pressure greater than 90 millimeters of mercury despite optimal medical management). Pediatric patients must have BP WNL for age. NOTE: blood pressure within the upper limit of normal is defined as: blood pressure less than or equal to the 95th percentile for age, height, and gender, and measured, and not be receiving medication for treatment of hypertension.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00942877

Contacts
Contact: Deborah E Allen, R.N. (301) 402-5640 allendeb@mail.nih.gov
Contact: Shivaani Kummar, M.D. (301) 435-0517 kummars@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: Agnes Strassberger    301-435-5664    agnes.strassberger@nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Shivaani Kummar, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00942877     History of Changes
Other Study ID Numbers: 090192, 09-C-0192
Study First Received: July 18, 2009
Last Updated: September 10, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
VEGF
Antiangiogenesis
Tyrosine Kinase Inhibitor
Advanced Cancer
Alveolar Soft Part Sarcoma
Sarcoma

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Alveolar Soft Part
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Cediranib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014