Activity of Sorafenib in Salivary Gland Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Salivary Gland Cancer
• Intervention / Treatment: Drug: Sorafenib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20133
    • IRCCS Istituto Nazionale Tumori

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	number of patients with adverse events	4 weeks

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Lisa Licitra, MD, Prof, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: April 6, 2012
• First Submitted That Met QC Criteria: October 8, 2012
• First Posted (Estimated): October 10, 2012

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Salivary gland metastatic recurrent disease clinical trial
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Salivary Gland Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: INT29/10