Clinical trial NCT02624128: Valproic Acid Plus Cisplatin and Cetuximab in Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck
Official title: Preclinical and Clinical Study of Valproic Acid Plus Cisplatin and Cetuximab in Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: head and neck cancer
valproic acid
recurrent
metastatic
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2015-12-08
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically proven squamous cell carcinoma of head and neck with exclusion of the nasopharynx
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 neutrophil 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 echocardiography with ejection fraction \> 50%)
11. Effective contraception for both male and female patients if the risk of conception exist
12. Signed written informed consent

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. Patient 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)l.
16. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.

Primary outcomes:
measure: Proportion of patients with an objective response
timeFrame: up to 4 years
Secondary outcomes:
measure: overall survival
timeFrame: up to 6 years
measure: time to tumor progression
timeFrame: up to 6 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: up to 18 weeks
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
Study officials:
affiliation: National Cancer Institute, Naples
name: Francesco Caponigro, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Alfredo Budillon, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Caponigro F, Di Gennaro E, Ionna F, Longo F, Aversa C, Pavone E, Maglione MG, Di Marzo M, Muto P, Cavalcanti E, Petrillo A, Sandomenico F, Maiolino P, D'Aniello R, Botti G, De Cecio R, Losito NS, Scala S, Trotta A, Zotti AI, Bruzzese F, Daponte A, Calogero E, Montano M, Pontone M, De Feo G, Perri F, Budillon A. Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial. BMC Cancer. 2016 Nov 25;16(1):918. doi: 10.1186/s12885-016-2957-y.