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

NCT00942877 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 09019209-C-0192
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sarcoma, Alveolar Soft Part

Keywords

VEGF; Antiangiogenesis; Tyrosine Kinase Inhibitor; Advanced Cancer; Alveolar Soft Part Sarcoma; Sarcoma

Outcome Measures

Primary Outcomes (4)

• Minimal Response Rate in Pediatric Participants With Alveolar Soft Part Sarcoma (ASPS)

  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)

  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)

• Number of Participants With a Response (Partial Response (PR) + Complete Response (CR)) of AZD2171 in Adult Participants With Alveolar Soft Part Sarcoma (ASPS)

  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.

  2 cycles (e.g., one cycle = 28 days)

• Number of Participants With a Best Observed Response

  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.

  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)

• Number of Participants With a Best Response

  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.

  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)

Secondary Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events

  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)

Study Arms (1)

Cediranib (AZD2171) Treatment

EXPERIMENTAL

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

Interventions

AZD2171 DRUG

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).

Also known as: Cediranib

Cediranib (AZD2171) Treatment

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Cohen JW, Widemann BC, Derdak J, Dombi E, Goodwin A, Dompierre J, Onukwubiri U, Steinberg SM, O'Sullivan Coyne G, Kummar S, Chen AP, Glod J. Cediranib phase-II study in children with metastatic alveolar soft-part sarcoma (ASPS). Pediatr Blood Cancer. 2019 Dec;66(12):e27987. doi: 10.1002/pbc.27987. Epub 2019 Sep 10.

  PMID: 31502400 DERIVED

• Hall PE, Shepherd STC, Brown J, Larkin J, Jones R, Ralph C, Hawkins R, Chowdhury S, Boleti E, Bahl A, Fife K, Webb A, Crabb SJ, Geldart T, Hill R, Dunlop J, McLaren D, Ackerman C, Wimalasingham A, Beltran L, Nathan P, Powles T. Radiological Response Heterogeneity Is of Prognostic Significance in Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor-targeted Therapy. Eur Urol Focus. 2020 Sep 15;6(5):999-1005. doi: 10.1016/j.euf.2019.01.010. Epub 2019 Feb 6.

  PMID: 30738795 DERIVED

• Powles T, Brown J, Larkin J, Jones R, Ralph C, Hawkins R, Chowdhury S, Boleti E, Bhal A, Fife K, Webb A, Crabb S, Geldart T, Hill R, Dunlop J, Hall PE, McLaren D, Ackerman C, Beltran L, Nathan P. A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK). Ann Oncol. 2016 May;27(5):880-6. doi: 10.1093/annonc/mdw014. Epub 2016 Jan 22.

  PMID: 26802156 DERIVED

• Kummar S, Allen D, Monks A, Polley EC, Hose CD, Ivy SP, Turkbey IB, Lawrence S, Kinders RJ, Choyke P, Simon R, Steinberg SM, Doroshow JH, Helman L. Cediranib for metastatic alveolar soft part sarcoma. J Clin Oncol. 2013 Jun 20;31(18):2296-302. doi: 10.1200/JCO.2012.47.4288. Epub 2013 Apr 29.

  PMID: 23630200 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part; Sarcoma

Interventions

cediranib

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Dr. Alice Chen
• Organization: National Cancer Institute

chenali@nih.gov

240-781-3274

Study Officials

• Alice P Chen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 18, 2009
• First Posted: July 21, 2009
• Study Start: July 18, 2009
• Primary Completion: September 30, 2018
• Study Completion: December 31, 2024
• Last Updated: March 3, 2025
• Results First Posted: April 27, 2021

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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).

Locations

US (1)