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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
King's College London
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesothelioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

First Posted
November 19, 2008
Last Updated
August 3, 2009
Sponsor
King's College London
Collaborators
Bayer
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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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