|First Submitted Date ICMJE||July 18, 2009|
|First Posted Date ICMJE||July 21, 2009|
|Last Update Posted Date||September 13, 2017|
|Start Date ICMJE||July 15, 2009|
|Estimated Primary Completion Date||July 31, 2019 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To determine if pediatric patients with ASPS will experience at least a minimal response rate when treated with AZD2171 [ Time Frame: 2 cycles ]|
|Original Primary Outcome Measures ICMJE
||To determine the response rate (PR + CR) of AZD2171 in patients with ASPS.|
|Change History||Complete list of historical versions of study NCT00942877 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma|
|Official Title ICMJE||Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma|
- To find out whether AZD2171 works in patients who have alveolar soft part sarcoma.
- Individuals 18 years of age and older who have been diagnosed with alveolar soft part sarcoma.
Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets. Cediranib (AZD2171), a VEGF/KIT tyrosine kinase inhibitor, has recently demonstrated antitumor activity in early phase clinical trials, which included 7 adult and 3 pediatric patients with ASPS.
To determine the response rate (PR + CR) of AZD2171 in adult patients with ASPS.
To compare gene expression profiles between pre-treatment and post-treatment biopsy specimens.
To determine if pediatric patients with ASPS will experience at least a minimal response rate when treated with AZD2171
Patients must have histologically or cytologically confirmed metastatic alveolar soft part sarcoma.
Less than 16 years old. BSA must be greater than or equal to 1.04 m2 and subject must be able to swallow tablets.
Adequate organ function.
Adult patients will be treated with AZD2171 at 30 mg by mouth once a day for 28 days (28-day cycles). Pediatric patients (< 16 years old) will be treated with 12 mg/m2/day once a day for 28 day (28-day cycles).
Blood pressure will be monitored weekly for the first 2 cycles then every 2 weeks for the remainder of the study (unless patients have experienced elevated blood pressure requiring drug therapy).
CT scans will be performed at baseline and every 2 cycles for restaging during the first 18
months; after 18 and 36 months, restaging CT scans will be performed every 3 or 4 cycles, respectively.
The study will be conducted using an optimal two-stage design in both pediatric and adult patients. The portion in adults will rule out an unacceptably low 5% clinical response rate (PR+CR) in favor of a modestly high response rate of 25%. In pediatric patients, the study will rule out an unacceptably low 5% overall clinical response rate (CR + PR) in favor of a higher response rate of 35%.
Optional biopsies will be performed in adult patients only at baseline and after 3-5 days of treatment (D3-D5) to evaluate early drug effect. A third optional biopsy after completion of 4 weeks of therapy (between C1D28 and C2D7) may be collected with the intention of providing further information about disease response to treatment. Depending on results of initial gene expression profiles, the timing of the biopsies may be adjusted, but without change in total number of biopsies per patient.
In a retrospective pilot study, CT scans from 20 consecutive off-study patients will be rereviewed. RECIST imaging measurements will be compared to volumetric density (Total Volume of Viable Tumor, TVVT) CT measurements. The objective is to establish whether volumetric density/percent necrosis algorithms such as TVVT more accurately assess extent of disease and response to therapy than standard RECIST criteria.
The total accrual ceiling is 73 participants (60 adult and 13 pediatric patients).
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Sarcoma, Alveolar Soft Part|
|Intervention ICMJE||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.
|Study Arms||Experimental: Treatment
Pediatric patients (<16 years old) will be treated with 12 mg/m2/day once a day for 28 days (28-day cycles).
Intervention: Drug: AZD2171
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Completion Date||July 31, 2019|
|Estimated Primary Completion Date||July 31, 2019 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
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:
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
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.
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.
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.
|Ages||up to 16 Years (Child)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00942877|
|Other Study ID Numbers ICMJE||090192
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 11, 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP