Back to resultsA Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung
Primary Purpose
Osteosarcoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Saracatinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteosarcoma focused on measuring AZD0530, Saracatinib, Osteosarcoma, Recurrent, Localized, to the Lung
Eligibility Criteria
Inclusion Criteria:
- Patient had recurrence of osteosarcoma, localized to the lungs, had complete surgical removal of all lung nodules are eligible for enrollment.
- Patient with suspected recurrence of osteosarcoma but who has not had surgery is eligible for enrollment but will not be randomized to receive study medication until deemed fully eligible following surgical removal of all lung nodules.
- Patient had histological confirmed diagnosis of osteosarcoma of the recurrent sample.
- Patient had recurrence of osteosarcoma in the lung following standard therapy including: adriamycin, cisplatin, ifosfamide and methotrexate.
- Patient is ≥ 15 and < 75 years of age.
- Weight ≥ 34 kg.
- ECOG performance score of 0-2.
- Adequate bone marrow function.
- Adequate renal function.
- Adequate hepatic function.
- Adequate cardiac function.
- Women of childbearing potential must have had a negative pregnancy test (urine or serum) ≤ 7 days prior to enrollment, and willingness to use an acceptable method of contraception during participation in the study and for 3 months after the last dose.
- Randomization must occur ≤ 6 weeks after complete surgical resection.
- Patient or legal guardian has signed informed consent.
Exclusion Criteria:
- Presence of metastatic disease in other locations in addition to the lung.
- Disruption of the lung pleura by tumor.
- Paget's disease.
- Patient currently using, or has previously used CYP3A4 inducers or inhibitors within 2 to 14 days prior to the initiation of oral therapy.
- Known hypersensitivity to other Src/Abl non-receptor kinase inhibitors.
- Evidence of interstitial lung disease.
- Any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
- Myocardial infarction within one year prior to study entry.
- Bleeding diathesis, resulting in symptomatic bleeding.
- Patient is pregnant or nursing/breast-feeding.
- Patient received chemotherapy, biological or investigational agent ≤ 28 days prior to enrollment.
- Patient experiencing unresolved toxicity ≥ CTCAE grade 2 (except alopecia) from previous agents.
Sites / Locations
- University of Alabama
- Children's Hospital Los Angeles
- USC/Norris Comprehensive Cancer Center and Hospital
- UCLA/Mattel's Children's Hospital
- Stanford University
- UCSF
- Sarcoma Oncology Center
- University of Florida
- University of Miami
- Indiana University
- University of Iowa Hospitals and Clinics
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
- National Cancer Institute
- Dana-Farber Cancer Institute
- University of Michigan
- Cincinnati Children's Hospital Medical Center
- St. Jude Children's Research Hospital
- Seattle Cancer Care Alliance/University of Washington Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Saracatinib
Placebo
Arm Description
Saracatinib will be administered as a once daily, oral dose of 175 mg, for a 28-day cycle, with no breaks between cycles. The duration of treatment with saracatinib will be 13 cycles.
Placebo will be administered as a once daily, oral dose of 175 mg, for a 28-day cycle, with no breaks between cycles. The duration of treatment with placebo will be 13 cycles.
Outcomes
Primary Outcome Measures
Progression Free Survival Rate Among Patients Treated With Saracatinib and Placebo.
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in progression free survival.
Secondary Outcome Measures
Change in Overall Survival With the Addition of Saracatinib to Pulmonary Metastasectomy, Versus Placebo and Pulmonary Metastasectomy
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in overall survival.
Change in Time to Treatment Failure With the Addition of Saracatinib to Pulmonary Metastasectomy, Versus Placebo and Pulmonary Metastasectomy
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in the time to treatment failure. Time to treatment failure is the time from randomization to treatment discontinuation.
Number of Genes Identified for Prediction of Recurrence of Osteosarcoma
To perform microarray analysis of tumor samples to identify a gene signature that predicts for recurrence of osteosarcoma using methodology that relies on preparation of RNA, followed by cDNA. Fluorescent labeling followed by hybridization to a DNA chip allows for quantitative scanning for hybridized complexes.
Biomarkers Related to Activation of Src and Src Substrates
To evaluate tumor samples for biomarkers related to activation of Src and Src substrates.
Cell Lines and Murine Xenografts From Recurrent Tumor Samples
To establish cell lines and murine xenografts from recurrent tumor samples.
Number of Mutations Identified That May be Causative For Recurrent Osteosarcoma
To perform sequencing analysis of DNA and RNA in tumor samples compared to normal blood to detect mutations that may be causative for recurrent osteosarcoma. The methodology uses transcriptome sequencing, exon re-sequencing and mate-pair end sequencing, allowing us to detect translocations. The availability of matched normal DNA in the blood will allow us to determine which changes are unique to the tumor.
Full Information
NCT ID
NCT00752206
First Posted
September 11, 2008
Last Updated
January 7, 2020
Sponsor
Sarcoma Alliance for Research through Collaboration
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT00752206
Brief Title
A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung
Official Title
A Randomized, Double-Blinded, Placebo-Controlled, Multi-Institutional, Cross-over, Phase II.5 Study of Saracatinib (AZD0530), a Selective Src Kinase Inhibitor, In Patients With Recurrent Osteosarcoma Localized to the Lung
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
The Data Safety Monitoring Board (DSMB) recommended study termination for slow accrual and futility.
Study Start Date
March 2009 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarcoma Alliance for Research through Collaboration
Collaborators
AstraZeneca
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine how long patients who undergo complete surgical removal of recurrent osteosarcoma in the lung will remain free of cancer after taking Saracatinib compared to patients taking placebo (a sugar pill).
Detailed Description
Further details provided by SARC (Sarcoma Alliance for Research through Collaboration):
After complete surgical removal of their cancer, patients will be randomly assigned to receive either Saracatinib or placebo (a sugar pill) throughout the study. Patients will take Saracatinib (or placebo) once daily by mouth for a total of 364 days. The duration of treatment is divided into 13 cycles, 28 days each cycle with no breaks in between.
Patients will be seen for interim medical history, physical exam and laboratory studies prior to each cycle. To monitor for recurrence of tumor, patients will undergo thoracic CT scans at 3-4 weeks, 6-8 weeks, at 3 months, at 6 months, at 9 months, at 12 months, then every 6 months up to 2 years, and then every year up to 5 years after starting treatment. An electrocardiogram (ECG) will be taken at 3 months, and a bone scan will be performed at 12 months.
Patients who recur in the lung while on-study and who are thought to be amenable to complete surgical resection will be able to find out if they were receiving placebo or saracatinib. Those patients who were receiving placebo may then have the option of undergoing surgical resection. If fully resected of all recurrent disease,they will be given the option of receiving oral therapy with saracatinib. Saracatinib will be administered as a once daily, oral dose of 175 mg, for a 28-day cycle, with no breaks between cycles. The duration of treatment with saracatinib will be thirteen 28-day cycles (364 days total). If complete resection of all lung nodules is not achieved, the patient will be removed from the study.
Patients who recur in locations other than the lung while on-study will be taken off study at that time.
Blood and tumor samples for research purposes will be collected at the time the tumor is removed.
After completing all 13 cycles, patients will be followed for approximately every 3 months until 2 years from starting treatment, then approximately every 6 months until 4 years from starting treatment, and once at year 5.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma
Keywords
AZD0530, Saracatinib, Osteosarcoma, Recurrent, Localized, to the Lung
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Saracatinib
Arm Type
Active Comparator
Arm Description
Saracatinib will be administered as a once daily, oral dose of 175 mg, for a 28-day cycle, with no breaks between cycles. The duration of treatment with saracatinib will be 13 cycles.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered as a once daily, oral dose of 175 mg, for a 28-day cycle, with no breaks between cycles. The duration of treatment with placebo will be 13 cycles.
Intervention Type
Drug
Intervention Name(s)
Saracatinib
Intervention Description
Oral Agent
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral Agent
Primary Outcome Measure Information:
Title
Progression Free Survival Rate Among Patients Treated With Saracatinib and Placebo.
Description
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in progression free survival.
Time Frame
Evaluation for recurrence/progression will be made every 3 months for the 1st year, then every 6 months up to 2 years, then every year up to 5 years after starting treatment.
Secondary Outcome Measure Information:
Title
Change in Overall Survival With the Addition of Saracatinib to Pulmonary Metastasectomy, Versus Placebo and Pulmonary Metastasectomy
Description
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in overall survival.
Time Frame
5 year overall survival
Title
Change in Time to Treatment Failure With the Addition of Saracatinib to Pulmonary Metastasectomy, Versus Placebo and Pulmonary Metastasectomy
Description
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in the time to treatment failure. Time to treatment failure is the time from randomization to treatment discontinuation.
Time Frame
Up to 12 months
Title
Number of Genes Identified for Prediction of Recurrence of Osteosarcoma
Description
To perform microarray analysis of tumor samples to identify a gene signature that predicts for recurrence of osteosarcoma using methodology that relies on preparation of RNA, followed by cDNA. Fluorescent labeling followed by hybridization to a DNA chip allows for quantitative scanning for hybridized complexes.
Time Frame
Up to 12 months
Title
Biomarkers Related to Activation of Src and Src Substrates
Description
To evaluate tumor samples for biomarkers related to activation of Src and Src substrates.
Time Frame
Up to 12 months
Title
Cell Lines and Murine Xenografts From Recurrent Tumor Samples
Description
To establish cell lines and murine xenografts from recurrent tumor samples.
Time Frame
Up to 12 months
Title
Number of Mutations Identified That May be Causative For Recurrent Osteosarcoma
Description
To perform sequencing analysis of DNA and RNA in tumor samples compared to normal blood to detect mutations that may be causative for recurrent osteosarcoma. The methodology uses transcriptome sequencing, exon re-sequencing and mate-pair end sequencing, allowing us to detect translocations. The availability of matched normal DNA in the blood will allow us to determine which changes are unique to the tumor.
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient had recurrence of osteosarcoma, localized to the lungs, had complete surgical removal of all lung nodules are eligible for enrollment.
Patient with suspected recurrence of osteosarcoma but who has not had surgery is eligible for enrollment but will not be randomized to receive study medication until deemed fully eligible following surgical removal of all lung nodules.
Patient had histological confirmed diagnosis of osteosarcoma of the recurrent sample.
Patient had recurrence of osteosarcoma in the lung following standard therapy including: adriamycin, cisplatin, ifosfamide and methotrexate.
Patient is ≥ 15 and < 75 years of age.
Weight ≥ 34 kg.
ECOG performance score of 0-2.
Adequate bone marrow function.
Adequate renal function.
Adequate hepatic function.
Adequate cardiac function.
Women of childbearing potential must have had a negative pregnancy test (urine or serum) ≤ 7 days prior to enrollment, and willingness to use an acceptable method of contraception during participation in the study and for 3 months after the last dose.
Randomization must occur ≤ 6 weeks after complete surgical resection.
Patient or legal guardian has signed informed consent.
Exclusion Criteria:
Presence of metastatic disease in other locations in addition to the lung.
Disruption of the lung pleura by tumor.
Paget's disease.
Patient currently using, or has previously used CYP3A4 inducers or inhibitors within 2 to 14 days prior to the initiation of oral therapy.
Known hypersensitivity to other Src/Abl non-receptor kinase inhibitors.
Evidence of interstitial lung disease.
Any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
Myocardial infarction within one year prior to study entry.
Bleeding diathesis, resulting in symptomatic bleeding.
Patient is pregnant or nursing/breast-feeding.
Patient received chemotherapy, biological or investigational agent ≤ 28 days prior to enrollment.
Patient experiencing unresolved toxicity ≥ CTCAE grade 2 (except alopecia) from previous agents.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Baird, MD
Organizational Affiliation
National Cancer Institute - Pediatric Oncology Branch
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center and Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Facility Name
UCLA/Mattel's Children's Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Sarcoma Oncology Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Seattle Cancer Care Alliance/University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.sarctrials.org
Description
Related Info
Learn more about this trial
A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung
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