Preoperative TPF Chemotherapy in Molecularly Selected Locally Advanced Resectable Oral Cavity Squamous Cell Cancer
Condition: Locally Advanced Resectable Oral Cavity Squamous Cell Cancer
MeSH terms: Neoplasms, Squamous Cell; Carcinoma, Squamous Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a phase II study of preoperative chemotherapy with docetaxel, cisplatin and
      5-fluorouracil (TPF) in locally advanced resectable oral cavity squamous cell cancer. The aim
      is to improve the rate of pathological complete response to induction chemotherapy in a
      molecular enriched population, consisting of patients with tumour harbouring a functional p53
      protein and/or showing low expression of beta-tubulin II.
    

Detailed description: 
      Patients with stage T2 (> 3 cm) T3 N1-N3 and T4a any N primary OCSCC are considered for
      enrolment in this trial. Patients will be asked to sign the informed consent for being
      admitted to the clinical study and in order to analyze the tumour biopsy. If a functional p53
      protein status and/or low expression of beta-tubulin II is identified, patient will be
      enrolled in therapeutic part of the study. In case of different molecular profile, patient
      will not be enrolled in the study. A radiological work up of disease is required before to
      start CT. A magnetic resonance imaging (MRI) with DWI, and if available, a dynamic contrast
      enhanced (DCE)-MRI will be performed before therapy.

      Each patient will receive induction CT, consisting of TPF (docetaxel 75 mg/sm and cisplatin
      80 mg/sm day 1 and 5 fluorouracil 800 mg/sm each day in continuous infusion day 1-4,
      according to Paccagnella et al, ASCO 2008) for 3 cycles every 21 days, followed by surgery.
      Prophylactic antibiotic with ciprofloxacin 500 mg 2 times/day will be administered starting
      from day 5th to day 15th after each cycle; G-CSF is admitted as secondary prophylaxis in case
      of febrile neutropenia or neutropenia grade 4 at previous cycle. Patient will have clinical
      examination at baseline and before each CT cycle. Whenever a clinical suspicion of
      progressing disease will exist, a radiological restaging with MRI will be performed and in
      case of radiological progression according to RECIST 1.1 the patient will be submitted to
      surgical excision of the tumour. However, in any case the investigators may 14 judge that the
      disease is progressing and they consider that chemotherapy is no more indicated, the patient
      will be submitted to surgery even without a radiological confirmation of progression. In case
      of clinical SD or PR, a radiological restaging will be planned with MRI and DWI-MRI at least
      two weeks after the third cycle (a DWI- MRI and, if available a DCE-MRI, will be performed
      after 1st cycle in order to evaluate early response imaging). Surgery will be performed
      within one month after the last cycle of CT, if there are no clinical contraindications.
      After the surgical treatment, adjuvant treatment will be delivered according to recognized
      pathological risk factors (Bernier J, 2005). Patients will be followed up according to the
      Institutional follow-up policy.
    

Intervention name(s): docetaxel, cisplatin, 5 fluorouracil
Intervention type(s): Drug
Other intervention name(s): taxotere, cisplatin, tolerak
Intervention MeSH terms: Cisplatin; Docetaxel; Fluorouracil
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: oral cavity cancer; induction chemotherapy; TP53; beta tubulin II