Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00942877 |
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Recruitment Status :
Active, not recruiting
First Posted : July 21, 2009
Results First Posted : April 27, 2021
Last Update Posted : March 12, 2024
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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 during cycles 1 and 2, then at the start of each subsequent cycle, 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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Sarcoma, Alveolar Soft Part | Drug: AZD2171 | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 53 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma |
| Actual Study Start Date : | July 18, 2009 |
| Actual Primary Completion Date : | September 30, 2018 |
| Estimated Study Completion Date : | December 31, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cediranib (AZD2171) Treatment
Adult participants will be treated with 30 mg by mouth once a day for 28 days (28-day cycles). Pediatric participants (<16 years old) will be treated with 12 mg/m^2/day once a day for 28 days (28-day cycles). |
Drug: AZD2171
Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with Alveolar Soft Part Sarcoma (ASPS).
Other Name: Cediranib |
- Minimal Response Rate in Pediatric Participants With Alveolar Soft Part Sarcoma (ASPS) [ Time Frame: Date treatment initiated to date off study, an average of 16.9 cycles for adult patients and 34.7 cycles for pediatric patients (1 cycle = 28 days) ]Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.0. A minimal response is defined as a 5% overall response rate (Partial Response (PR) + Complete Response (CR)
- Number of Participants With a Response (Partial Response (PR) + Complete Response (CR)) of AZD2171 in Adult Participants With Alveolar Soft Part Sarcoma (ASPS) [ Time Frame: 2 cycles (e.g., one cycle = 28 days) ]Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all no-target lesions and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
- Number of Participants With a Best Observed Response [ Time Frame: Participants were followed for the duration of treatment, an average of 16.9 cycles for adult patients and 34.7 cycles for pediatric patients (1 cycle = 28 days) ]Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response is disappearance of all target lesions and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease is at least a 20% increase in the sum of the LD of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
- Number of Participants With a Best Response [ Time Frame: Date treatment initiated to date off study, an average of 16.9 cycles for adult patients and 34.7 cycles for pediatric patients (1 cycle = 28 days) ]Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response is disappearance of all target lesions and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease is at least a 20% increase in the sum of the LD of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
- Number of Participants With Serious and Non-serious Adverse Events [ Time Frame: Participants were followed for the duration of treatment, an average of 16.9 cycles for adult patients and 34.7 cycles for pediatric patients (1 cycle = 28 days) ]Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | up to 16 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
- 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 computed tomography (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 principal investigator's (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., vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors or bevacizumab). Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery.
Body surface area (BSA) greater than or equal to 1.04 square meter.
Eastern Cooperative Oncology Group (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
- Aspartate aminotransferase (AST)(Serum glutamic Oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (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 milliliter/min for adults or greater than or equal to 60 milliliter/min/1.73m^2 for children with creatinine levels above institutional upper limit of normal.
Corrected QT interval (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 27%.
At present, the potential of Cediranib (AZD2171) for clinically significant drug interactions involving the cytochrome P450 (CYP) isozymes is unknown. However, studies of the agent in rats indicated possible suppression of cytochrome P450, family 1, subfamily A (CYP1A) that may be of biological significance. Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity of pharmacokinetics (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 vascular endothelial growth factor (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 Q wave, T wave (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.
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with AZD2171.
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 blood pressure (BP) within normal limits (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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00942877
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | |
| Bethesda, Maryland, United States, 20892 | |
| Principal Investigator: | Alice P Chen, M.D. | National Cancer Institute (NCI) |
Documents provided by Alice Chen, M.D., National Cancer Institute (NCI):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Alice Chen, M.D., Principal Investigator, National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00942877 |
| Other Study ID Numbers: |
090192 09-C-0192 |
| First Posted: | July 21, 2009 Key Record Dates |
| Results First Posted: | April 27, 2021 |
| Last Update Posted: | March 12, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | All individual participant data (IPD) will be shared with intramural investigators upon request. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
| Time Frame: | Clinical data available during the study and indefinitely. |
| Access Criteria: | Clinical data will be made available via subscription to Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Additionally, requests for all collected individual participant data (IPD) from clinical trials, conducted under a binding collaborative agreement between National Cancer Institute (NCI)/Division of Cancer Treatment and Diagnosis (DCTD) and a pharmaceutical/biotechnology company, that are not under data safety monitoring board (DSMB) monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) Director in conjunction with the NCI/DCTD Regulatory Affairs Branch). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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VEGF Antiangiogenesis Tyrosine Kinase Inhibitor |
Advanced Cancer Alveolar Soft Part Sarcoma Sarcoma |
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Sarcoma Sarcoma, Alveolar Soft Part Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Neoplasms, Muscle Tissue |
Cediranib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |