Preclinical and clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of head and neck

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; Recurrent and/or metastatic squamous cell carcinoma of head and neck; MedDRA version: 17.0Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2014-001523-69-IT
• Lead Sponsor: Istituto Nazionale Tumori di Napoli - Fondazione G. Pascale

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-05
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

1.Histologically or cytologically proven HPV negative squamous cell carcinoma of head and neck with the exclusion of nasopharyngeal cancer
2.First-line recurrent and/or metastatic disease
3.No prior chemotherapy except for chemoradiation or induction chemotherapy followed by local treatment given in the context of a curative strategy.
4.age> 18 years
5.ECOG Performance Status =1
6.Life expectancy at least 3 months at study entrance
7.Normal bone marrow reserve (absolute neuthrophil count > 1500/mm3; platelets > 100000/mm3; haemoglobin> 9 g/dl)
8.Normal hepatic function (total serum bilirubin < 1.5 x upper limit of normal; liver transaminases < 3 x upper limit of normal)
9.Normal renal function (serum creatinine < 1,25 x upper limit of normal and creatinine clearance > 60 ml/min).
10.Normal cardiac function (assessed by ECG and ecocardiography with ejection fraction > 50%)
11.Effective contraception for both male and female patients if the risk of conception exists.
12.Signed written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

1. Concomitant treatment with other experimental drugs.
2. Brain metastases (CT scan or MRI required only in case of clinical suspicion of CNS metastases)
3. Non squamous cell histology
4. Any concurrent malignancy. Patients with a previous malignancy but without evidence of disease for 5 years will be allowed to enter the trial.
5. History of myocardial infarction within the last 12 months
6. ECOG PS = 2
7. Significant cardiovascular comorbidity (e.g. myocardial infarction, superior vena cava [SVC] syndrome, patients with an ejection fraction of <50%) or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
8. History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc.
9. HIV positive patients
10. Patients who cannot take oral medication, who require intravenous feeding, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
11. Known or suspected hypersensitivity to any of the study drugs.
12. Patients who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.
13. Major surgical procedure, within 28 days prior to study treatment start.
14. Pregnant or lactating women.
15. Women of childbearing potential with either a positive or no pregnancy test at baseline (postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).
16. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To explore in a phase 2 trial whether the addition of valproic acid to the standard cisplatin-cetuximab combination can improve treatment activity (in terms of objective response rate) in patients with recurrent/metastatic non pretreated SCCHN;Secondary Objective: •To evaluate the impact of the experimental schedule on:<br>•Time to progression<br>•Overallsurvival (OS).<br>•Toxicity.<br>•Quality of life<br>•ParallelPreclinicalstudy<br>•Biomarker studies on tumor and blood samples<br>;Primary end point(s): The overall response rate;Timepoint(s) of evaluation of this end point: 24 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Time to progression, duration of response and overall survival will be calculated from the first treatment day until the day of event occurrence;Timepoint(s) of evaluation of this end point: from the first treatment day until the day of event occurrence