OsteosarcomaPhase 2NCT00752206
A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung
A Phase 2 study testing Saracatinib in people with Osteosarcoma, run by Sarcoma Alliance for Research through Collaboration at 18 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 15 to 74 years
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- Saracatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 18 sitesUnited States
- Study dates
- Mar 2009to Dec 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 74 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
University of Michigan
Ann Arbor, Michigan, 48106
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
National Cancer Institute
Bethesda, Maryland, 20892
University of Alabama
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Florida
Gainesville, Florida, 32610
Indiana University
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Children's Hospital Los Angeles
Los Angeles, California, 90027
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90089
UCLA/Mattel's Children's Hospital
Los Angeles, California, 90095
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami
Miami, Florida
Stanford University
Palo Alto, California, 94304
UCSF
San Francisco, California, 94143
Sarcoma Oncology Center
Santa Monica, California, 90403
Seattle Cancer Care Alliance/University of Washington Medical Center
Seattle, Washington, 98109
About this study
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
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).
Read the 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.
- Conditions
- Osteosarcoma
- Being tested
- Saracatinib, Placebo
- Keywords
- AZD0530, Saracatinib, Osteosarcoma, Recurrent, Localized, to the Lung
- Medical subject headings
- Osteosarcoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaracatinibDrug
Oral Agent
PlaceboDrug
Oral Agent
| Study group | Role | What they receive |
|---|---|---|
| Saracatinib | Active comparator | 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. Receives: Drug: Saracatinib |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (6)
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.
Measured: 5 year 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.
Measured: Up to 12 months
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.
Measured: Up to 12 months
Biomarkers Related to Activation of Src and Src Substrates
To evaluate tumor samples for biomarkers related to activation of Src and Src substrates.
Measured: Up to 12 months
Cell Lines and Murine Xenografts From Recurrent Tumor Samples
To establish cell lines and murine xenografts from recurrent tumor samples.
Measured: Up to 12 months
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.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2008 (estimated)
- Study startMar 2009
- Primary completionAug 2017
- Study completionDec 2017
Why it stopped: The Data Safety Monitoring Board (DSMB) recommended study termination for slow accrual and futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Kristin Baird, MD, Principal investigator, National Cancer Institute - Pediatric Oncology Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00752206
- Sponsor's protocol ID
- SARC012
- Other IDs
- D8180C00039
- Status last verified
- Apr 2019
- First submitted
- 11 Sep 2008
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00752206
- Acronym / sponsor ID
- SARC012
- Conditions
- Osteosarcoma
- Keywords
- AZD0530, Saracatinib, Osteosarcoma, Recurrent, Localized, to the Lung
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Data Safety Monitoring Board (DSMB) recommended study termination for slow accrual and futility.
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Sarcoma Alliance for Research through CollaborationUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Mar 2009 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 15 Sep 2008 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saracatinib | Active comparator | Drug: SaracatinibSaracatinib 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 | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 15 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SaracatinibOral Agent | Drug | Saracatinib |
| PlaceboOral Agent | Drug | Placebo |
Primary outcome
Progression Free Survival Rate Among Patients Treated With Saracatinib and Placebo.
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.
To determine if the addition of saracatinib to pulmonary metastasectomy, versus placebo and pulmonary metastasectomy, results in a change in progression free survival.
6 secondary outcomes
Change in Overall Survival With the Addition of Saracatinib to Pulmonary Metastasectomy, Versus Placebo and Pulmonary Metastasectomy
Time frame: 5 year overall survival
Change in Time to Treatment Failure With the Addition of Saracatinib to Pulmonary Metastasectomy, Versus Placebo and Pulmonary Metastasectomy
Time frame: Up to 12 months
Number of Genes Identified for Prediction of Recurrence of Osteosarcoma
Time frame: Up to 12 months
Biomarkers Related to Activation of Src and Src Substrates
Time frame: Up to 12 months
Cell Lines and Murine Xenografts From Recurrent Tumor Samples
Time frame: Up to 12 months
Number of Mutations Identified That May be Causative For Recurrent Osteosarcoma
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristin Baird, MD principal investigator
National Cancer Institute - Pediatric Oncology Branch
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Saracatinib in people with Osteosarcoma, run by Sarcoma Alliance for Research through Collaboration at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival Rate Among Patients Treated With Saracatinib and Placebo. (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.