Patients with localled advanced or metastatic thyroid cancer . histological sub-types will include differentiated and medullary thyroid cancer.
Conditions
Interventions
Trade Name: Nexavar
Product Name: Nexavar
Pharmaceutical Form: Film-coated tablet
Sponsors
Royal Marsden Nhs Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Human subjects with advanced / metastatic differentiated or medullary thyroid carcinoma 2. Patients must have one of the following histological sub-types - Any papillary subtypes including follicular variants, tall cell, columnar cell and diffuse sclerosing, - Any follicular, hurthle cell or medullary 3. Patients must be deemed not suitable for radio active iodine therapy 4. Must have uni-dimensional measurable disease on CT or MRI according to Response Evaluation Criteria of Solid tumours (RECIST) 5. Lesions which are accessible for low risk biopsy 6. Male/female subjects age 18 years or greater 7. Patients with ECOG performance status 0, 1 see appendix 3 8. Life expectancy greater than 12 weeks 9. The cognitive capacity to understand patient information sheets and give written informed consent and be able to comply with follow up requirements 10. Women must be post-menopausal (no menstrual period for at least a year) or have a negative pregnancy serum test on entry into the study (even if surgically sterilized) Patients must refrain from becoming pregnant throughout their treatment and for upto 6 months after stopping study drug. They must be on adequate contraception (abstinence, oral contraceptives, barrier method with spermicide, implantable or injectable contraceptive or surgical sterilization) throughout this period. Patients must have adequate renal, liver and haematological function 11 Serum creatinine = 1.5 x ULN 12. Serum aspartate transaminase and alanine transaminase = 2.5 x ULN 13. Total serum bilirubin = 1.5 x ULN 14. Amylase and lipase =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A patient will not be eligible for inclusion in this study if any of the following apply 1. Anaplastic and poorly differentiated carcinoma of the thyroid 2. Previous malignancy except cervical cis, Basal cell carcinoma or superficial bladder cancer 3. Patients with recent or active bleeding diathesis 4. HIV infection or chronic Hepatitis B or C 5. Concomitant rifampicin and Hypericum perforatum also known as St. John’s wort 6. Patients with congestive heart failure greater than NYHA functional class II (symptomatic during ordinary activity; (see Appendix 5) 7. Patients with cardiac arrhythmias greater than Grade 1 NCI CTCAE, Version 3.0 (see appendix 2) (conduction abnormality and supraventricular arrhythmia present but patient is asymptomatic, intervention not indicated, palpitations present and QTc > 0.45-0.47 second). 8. Patients with active coronary artery disease or ischemia. 9. Patients with Child-Pugh class C hepatic impairment (see appendix 4) 10. Patients with severe renal impairment (calculated creatinine clearance of 6 months. In the case of a solitary brain metastasis, evidence of a disease-free interval of at least 3 months post surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days 13. Previous treatment with a tyrosine kinase inhbitor or anti-angiogenic agent (licensed or investigational) such as sunitinib or bevacizumab 14. Any drug (licensed or investigational) that targets the RAS, VEGF, VEGFR or EGFR pathway 15. Significant surgery within 4 weeks of start of study 16. Investigational drug therapy during or within 30 days 17. Any cancer chemotherapy, immunotherapy, radiotherapy or hormonal treatment over the last 4 weeks. Palliative radiotherapy to symptomatic disease sites is permitted Concurrent anti-cancer chemotherapy, immunotherapy or hormonal therapy except biphosphanates 18. Women who are pregnant, breast feeding, or planning pregnancy within 6 months after the last treatment (this includes men who plan to father a child within 6 months of the last treatment) 19. History of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results 20. Recent thromboembolic events including MI 21. Need for anti-coagulant therapy (except low dose aspirin)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary endpoints will be - proportion of patients achieving a response during 9 and 12 months of treatment with sorafenib - biomarkers - toxicity outcomes at 1,3,6,9 and 12 months - progression free and overall survival ; Primary end point(s): The primary efficacy endpoint of the study is the proportion of patients that have achieved a response during 6 months of treatment with the study drug. The best overall response (BOR) for each patient is the best ‘objective overall response’ (ORR) recorded on CRF from the start of treatment until 6 months of treatment with the study drug has been completed. The efficacy variable ORR will be determined on CT/MRI evaluation and biochemical results using the modified RECIST criteria. The proportion of patients that have achieved a response will be the sum of the BOR (only CR, CRu and PR) as a percentage of all patients. ;Main Objective: The primary endpoint will be the the proportion of patients that have achieved a response during 6 months of treatment with sorafenib tosylate for thyroid cancer. | — |
Countries
United Kingdom
Outcome results
None listed