Activity of Sorafenib in Salivary Gland Cancer

Study Overview
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Brief Summary
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This is a single agent, prospective, open-label, monocenter, phase II trial of sorafenib in patients with recurrent and/or metastatic salivary gland carcinoma. This trial will be conducted with the primary aim to determine the response rate (CR+PR) according to the RECIST criteria. Response rate according to CHOI criteria, correlation between CHOI criteria and outcome, disease Control Rate (DCR) and acute toxicity will be evaluated as secondary objectives.

Detailed Description
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This phase II trial was conducted on adult patients with RMSGC. Inclusion criteria were as follows: histologically proven diagnosis of RMSGC; availability of primary tissue (block or formalin fixed paraffin embedded [FFPE] tissue slides); age _18 years; Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0e1; adequate bone marrow, liver and renal function (haemoglobin >9.0 g/dl; neutrophil count >1500/mm3; platelet count _100,000/ml; total bilirubin <1.5 _ upper limit of normal [ULN]; ALT and AST <2.5 _ ULN and <5 _ ULN for patients with liver metastases; serum creatinine <1.5 _ ULN; alkaline phosphatase <4 _ ULN; PT-INR/PTT <1.5 _ ULN); _1 measurable unidimensional lesion by magnetic resonance imaging (MRI) or computed tomography (CT) scan according to the RECIST 1.1 criteria. Patients with cardiac disease (i.e. congestive heart failure New York Heart Association (NYHA) > 2, cardiac arrhythmia; uncontrolled hypertension) in the six months before study entry were excluded. Previous chemotherapy for metastatic disease was allowed and progression of disease was not required for the enrolment. All patients provided written informed consent. The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by the local Ethical Committee (Registry number, NCT01703455). 2.2. Treatment and assessments: Patients received 400 mg of sorafenib orally every 12 h on a continuous basis in 4-week cycles until disease progression and/or unacceptable toxicity. Biochemical and clinical evaluation, and drug safety monitoring according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were performed every 4 weeks. The attribution of adverse events (AEs) to the study drug was judged by the investigators. CT scans were performed every 8 weeks until disease progression. An independent evaluation of radiological response (RECIST and Choi criteria) was performed by two radiologists on anonymised CT scans. Stomatology evaluation was performed at baseline to exclude any sign of osteoradionecrosis. Dose reduction was adopted in cases of clinically significant haematologic or other AEs that were considered related to sorafenib. In such cases, doses were reduced to 400 mg once daily and then to 400 mg every other day. If further reductions were required, patients were withdrawn from the trial. Dose reescalation was not allowed.

Official Title
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Sorafenib in Recurrent and/or Metastatic Salivary Gland Carcinomas: Phase II Study

Conditions
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Salivary Gland Cancer

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven relapsed and/or metastatic salivary gland cancer for which potentially curative options such as surgery or radiotherapy are not indicated One target lesion measurable by CT-scan or MRI according to RECIST criteria Age + 18 years ECOG 0 or 1 Adequate bone marrow, liver and renal function Signed written informed consent Exclusion Criteria: Symptomatic metastatic brain or meningeal tumors History of cardiac disease such as congestive heart failure>NYHA class 2 Active CAD Cardiac arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension Pregnant or breast-feeding patient Patients with evidence or history of bleeding diathesis Patients undergoing renal dialysis Patients unable to swallow oral medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib 400 mg twice daily<br>Sorafenib 400 mg twice daily, on a continuous basis (each morning and evening), in 4 week cycles | Drug: Sorafenib<br>* 400 mg twice daily, on a continuous basis (each morning and evening), in 4 week cycles<br>* Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response | Response Rate according to RECIST criteria. Response will be evaluated every 2 months. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate according to CHOI criteria | assessment of tumor response according to CHOI criteria | 8 weeks | 
| correlation between CHOI criteria and outcome | correlation between CHOI criteria and survival (OS and PFS) | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Salivary gland metastatic recurrent disease clinical trial