Valproic Acid Plus Cisplatin and Cetuximab in Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck (V-CHANCE)

National Cancer Institute, Naples

Status and phase

Active, not recruiting

Phase 2

Conditions

Squamous Cell Carcinoma of the Head and Neck

Treatments

Drug: Cisplatin

Drug: Cetuximab

Drug: Valproic Acid

Study type

Interventional

Funder types

Other

Identifiers

NCT02624128

2014-001523-69 (EudraCT Number)

V-CHANCE

Details and patient eligibility

About

V-CHANCE is a phase 2, trial exploring the feasibility and the activity of valproic acid (VPA) in combination with the standard cisplatin-cetuximab combination in patients with recurrent/metastatic squamous cell carcinoma of the head and neck, never treated with first-line chemotherapy. The study includes an explorative analysis of the potential prognostic or predictive role of several biomarkers with the aim of improving the knowledge of the mechanisms by which VPA enhances chemotherapy effect and of identifying early predictors of treatment response/resistance.

Enrollment

39 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

Concomitant treatment with other experimental drugs.
Brain metastases (CT scan or MRI required only in case of clinical suspicion of CNS metastases)
Non squamous cell histology
Any concurrent malignancy. Patient with a previous malignancy but without evidence of disease for 5 years will be allowed to enter the trial.
History of myocardial infarction within the last 12 months
ECOG PS ≥ 2
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.
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.
HIV positive patients
Patients who cannot take oral medication, who require intravenous feeding, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
Known or suspected hypersensitivity to any of the study drugs.
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.
Major surgical procedure within 28 days prior to study treatment start.
Pregnant or lactating women.
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)l.
Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.