Estudio de fase III, aleatorizado y en doble ciego, de evaluación de la eficacia y la seguridad de sorafenib en comparación con placebo en el cáncer de tiroides diferenciado refractario al yodo radiactivo localmente avanzado/metastáticoA Double-Blind, Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

Phase 1

• Conditions: Cancer diferenciado de TiroidesDifferentiated thyroid cancer; MedDRA version: 12.0Level: LLTClassification code 10016935Term: Follicular thyroid cancer; MedDRA version: 12.0Level: LLTClassification code 10033701Term: Papillary thyroid cancer; MedDRA version: 12.0Level: LLTClassification code 10055107Term: Thyroid cancer metastatic; MedDRA version: 12.0Level: LLTClassification code 10066136Term: Huerthle cell carcinoma

• Registration Number: EUCTR2009-012007-25-ES
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-25
• Last Update Posted: 11 December 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

- Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular and Hurthle cell)
- Progression within 14 months (RECIST should be used as a basis for the assessment of disease progression)
- RAI refractory: patients will be deemed to be refractory to radioactive iodine (RAI) if they have a known tumor lesion that qualifies as a target lesion per the protocol RECIST criteria, and that target lesion has no iodine uptake on a post-radioactive-iodine scan performed under conditions of a low iodine diet and adequate TSH elevation or rhTSH stimulation.
Certain patients whose tumors have iodine uptake may also be eligible for participation. They include the following categories of patients:
Patients who have some iodine uptake, who have had a radioactive iodine treatment (>=100 mCi) within the last 16 months, and who have had progression (by RECIST) of their target lesion(s) despite that RAI treatment (which was performed under conditions of a low iodine diet and adequate TSH elevation or rhTSH stimulation);
OR
Patients who have some iodine uptake, who have had multiple RAI treatments, whose last RAI treatment was >16 months ago, and who had progression after each of two RAI treatments (>=100 mCi each) that were done within 16 months of each other (and which were each performed under conditions of a low iodine diet and adequate TSH elevation or rhTSH stimulation);
OR
Any individual patient who has received RAI treatments with a cumulative RAI dose of >=600 mCi.
- Not a candidate for surgery or radiotherapy with curative intent
- Subjects with at least one measurable lesion. Lesions must be measured by CT-scan or MRI (Magnetic Resonance Imaging) according to Response Evaluation Criteria in Solid Tumors [RECIST Criteria (v1.0), see Appendix 10.6].
For this study, bone lesions are considered to be measurable and eligible as target lesions if they are lytic lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that can be evaluated by CT or MRI and the soft tissue component meets the definition of measurability according to RECIST (vs. 1.0).
- Availability of histological material for central review of the diagnosis of differentiated thyroid cancer
- Adequate TSH-suppression (< 0.5 mU/l)
- Age > 18 years
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to randomization:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count >= 100,000/mm3
- Total bilirubin < 1.5 times the upper limit of normal
- Alanine aminotransaminase (ALT) and Aspartate aminotransferase (AST) < 2.5 x upper limit of normal
- Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN)
- Serum creatinine < 1.5 x ULN.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Life expectancy of at least 12 weeks.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
- Women and men of childbearing potential must agree to use adequate contraception (barrier method of birth control) since signing of the informed consent form until at least 30 days after the last study drug administration.
- Subject

Exclusion Criteria

- Histologic subtypes of thyroid cancer other than differentiated (i.e. like anaplastic and medullary carcinoma, lymphoma or sarcoma).
- Prior anticancer treatment with tyrosine kinase inhibitors, monoclonal antibodies (licensed or investigational) that target VEGF or VEGF Receptors or other targeted agents.
- Prior anti-cancer treatment for thyroid cancer with use of chemotherapy (low dose chemotherapy for radiosensitization is allowed) or Thalidomide or any of its derivatives.
- Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization.
- Non-healing wound, ulcer, or bone fracture.
- Evidence or history of bleeding diathesis or coagulopathy disorder.
- Subjects with tracheal, bronchial or esophageal infiltration with significant risk of bleeding but without having received local treatment prior to enrollment in the study.
- Clinically significant cardiac disease including congestive heart failure > class II New York Heart Association (NYHA) (see Appendix 10.5), unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction within the past 6 months prior to randomization.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management.
- Thrombotic or embolic venous or arterial events, such as a cerebrovascular accident, including transient ischemic attacks, arterial thrombosis, deep vein thrombosis and pulmonary embolism within the past 6 months.
- Hemorrhage/bleeding event National Cancer Institute NCI-Common Terminology Criteria for Adverse Events (CTCAE) greater than or equal to Grade 3 within 3 months of randomization.
- Infection > NCI-CTCAE (version 3) Grade 2.
- Known human immunodeficiency virus infection or infection with hepatitis B or C.
- Previous or concurrent cancer that is distinct in primary site or histology from thyroid cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma and superficial bladder tumors [Ta (Non invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
- Known or suspected allergy to sorafenib or hypersensitivity to sorafenib or any agent given in the course of this trial.
- Subjects with seizure disorder requiring medication (such as steroids or anti-epileptics).
- Subjects undergoing renal dialysis.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
- Unresolved toxicity (i.e. neurotoxicity) attributed to any prior therapy higher than NCI-CTCAE (version 3) Grade 2 (excluding cases of alopecia).
- Any malabsorption condition.
- Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
History of brain metastases: allowed, provided definitive therapy (surgery and/or radiation) has been administered before randomization , no further treatment of brain metastases is planned, the subject is clinically stable for at least 2 weeks before study treatment (Prior and ongoing corticosteroid treatment is allowed, provided the dose is not high, stable and no dose adjustments are needed after randomization).
Pregnant or breast-feeding subjects: Women of childbearing potential must have a negative pregnancy test performed within 7 days

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified