Sorafenib in Previously Treated Malignant Mesothelioma (SMS)
Primary Purpose
Mesothelioma
Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Sorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Mesothelioma
Eligibility Criteria
Inclusion Criteria:
- Malignant pleural or peritoneal mesothelioma previously treated with first line platinum-based chemotherapy (prior pemetrexed not required)
- Not suitable for radical resection. Prior radical or cytoreductive surgery allowed
- Age >18 years
- ECOG performance status 0-2
- Measurable disease. Lesions must be measured by CT scan or MRI according to modified RECIST (Appendix B)
- Life expectancy of at least 12 weeks
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
- haemoglobin ≥ 9.0 g/dL
- neutrophil count ≥ 1.5 x109/L
- platelet count ≥ 100 x109/L
- total bilirubin ≤ 1.5 x upper limit of normal
- ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for *alkaline phosphatase ≤ 4 x upper limit of normal
- PT-INR (international normalized ratio of PT) / PTT ≤1.5 x upper limit of normal
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures.
Exclusion Criteria:
- History of cardiac disease: congestive heart failure > NYHA (New York Heart Association) class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted); or uncontrolled hypertension (defined as systolic blood pressure >150mmHg or diastolic pressure >90mmHg despite optimal medical management)
- Impaired immunity or chronic infection including history of HIV (human immunodeficiency virus) infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 NCI-CTCAE version 3.0)
- Seizure disorder requiring medication (such as steroids or anti-epileptics)
- Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
- History of organ allograft
- Evidence or history of bleeding diathesis or coagulopathy;
- Renal dialysis
- Cancer other than mesothelioma within 5 years prior to start of study treatment EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumours [Ta (noninvasive tumour), Tis (carcinoma in situ) & T1 (tumour invading lamina propria)]
- Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
- Pulmonary haemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
- Any other haemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
- Serious, non-healing wound, ulcer, or bone fracture
- Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Known or suspected allergy to the investigational agent or any agent given in association with this trial
- Any condition that is unstable or could jeopardise the safety of the patient and their compliance in the study
- Patients unable to swallow oral medications
- Any malabsorption condition.
- Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for malignant mesothelioma, other than first line platinum-based combination chemotherapy
- Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section)
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug (bronchoscopy is allowed)
- Granulocyte colony stimulating factor (GCSF) or granulocyte macrophage colony stimulating factor (GMCSF), within 3 weeks of study entry
- Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin (1 mg po OD) is permitted if the INR (international normalized ratio) is < 1.5. Low-dose aspirin is permitted (≤ 81 mg daily)
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry.
Sites / Locations
- Guy's and St Thomas' NHS Foundation Trust
Outcomes
Primary Outcome Measures
Progression-free survival
Secondary Outcome Measures
Response rate as assessed with CT scan
Overall survival
Change in FDG-PET avidity
Full Information
NCT ID
NCT00794859
First Posted
November 19, 2008
Last Updated
August 3, 2009
Sponsor
King's College London
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00794859
Brief Title
Sorafenib in Previously Treated Malignant Mesothelioma
Acronym
SMS
Official Title
Trial of Sorafenib in Malignant Mesothelioma Previously Treated With Platinum-based Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2009
Overall Recruitment Status
Unknown status
Study Start Date
October 2008 (undefined)
Primary Completion Date
December 2009 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
King's College London
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The principal objective of the study is to investigate the effect of sorafenib on progression free survival (time until the cancer begins to grow again,) in patients with malignant mesothelioma who have had prior treatment with chemotherapy. Effectiveness of the drug will also be explored with PET scans before and during treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
400mg twice daily
Primary Outcome Measure Information:
Title
Progression-free survival
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Response rate as assessed with CT scan
Time Frame
2 months
Title
Overall survival
Time Frame
Median
Title
Change in FDG-PET avidity
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Malignant pleural or peritoneal mesothelioma previously treated with first line platinum-based chemotherapy (prior pemetrexed not required)
Not suitable for radical resection. Prior radical or cytoreductive surgery allowed
Age >18 years
ECOG performance status 0-2
Measurable disease. Lesions must be measured by CT scan or MRI according to modified RECIST (Appendix B)
Life expectancy of at least 12 weeks
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
haemoglobin ≥ 9.0 g/dL
neutrophil count ≥ 1.5 x109/L
platelet count ≥ 100 x109/L
total bilirubin ≤ 1.5 x upper limit of normal
ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for *alkaline phosphatase ≤ 4 x upper limit of normal
PT-INR (international normalized ratio of PT) / PTT ≤1.5 x upper limit of normal
Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures.
Exclusion Criteria:
History of cardiac disease: congestive heart failure > NYHA (New York Heart Association) class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted); or uncontrolled hypertension (defined as systolic blood pressure >150mmHg or diastolic pressure >90mmHg despite optimal medical management)
Impaired immunity or chronic infection including history of HIV (human immunodeficiency virus) infection or chronic hepatitis B or C
Active clinically serious infections (> grade 2 NCI-CTCAE version 3.0)
Seizure disorder requiring medication (such as steroids or anti-epileptics)
Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
History of organ allograft
Evidence or history of bleeding diathesis or coagulopathy;
Renal dialysis
Cancer other than mesothelioma within 5 years prior to start of study treatment EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumours [Ta (noninvasive tumour), Tis (carcinoma in situ) & T1 (tumour invading lamina propria)]
Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
Pulmonary haemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
Any other haemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
Serious, non-healing wound, ulcer, or bone fracture
Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Known or suspected allergy to the investigational agent or any agent given in association with this trial
Any condition that is unstable or could jeopardise the safety of the patient and their compliance in the study
Patients unable to swallow oral medications
Any malabsorption condition.
Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for malignant mesothelioma, other than first line platinum-based combination chemotherapy
Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section)
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug (bronchoscopy is allowed)
Granulocyte colony stimulating factor (GCSF) or granulocyte macrophage colony stimulating factor (GMCSF), within 3 weeks of study entry
Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin (1 mg po OD) is permitted if the INR (international normalized ratio) is < 1.5. Low-dose aspirin is permitted (≤ 81 mg daily)
Investigational drug therapy outside of this trial during or within 4 weeks of study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Spicer, MRCP, PhD
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
12. IPD Sharing Statement
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Sorafenib in Previously Treated Malignant Mesothelioma
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