Surgery Vs Chemoradiation for Oropharyngeal Cancer- A Phase II/III Integrated Design Randomized Control Trial

Prior treatment

• Prior head and neck malignancy
• Prior chemotherapy for a different cancer administered within 3 years prior to registration
• Patients who have received any neoadjuvant/ induction chemotherapy
• Prior radiotherapy to the region of the head and neck that would result in overlap of radiation therapy fields
• Presence of previous episode of thrombosis or embolism or presence of a prothrombotic condition in last 1 year
• Prior allergic reaction to cisplatin
• Patients on other investigational drugs within last 30 days

Other illness

• Prior invasive malignancy, unless disease free for a minimum of 3 years
• Unresectable primary or nodal disease involving the carotid vessels, prevertebral fascia or skull base

Lab values

• Calculated GFR \< 50 cc/min
• Patients who have uncontrolled cardiac comorbidity
  • QTc prolongation (a value of \>450 milliseconds)
  • Ejection fraction below 50%
  • Presence of regional wall akinesia
• Severe active co-morbidities such as severe cardiac failure, severe pulmonary compromise, type 1or 2 diabetes mellitus (Hb1ac of \> 8 mg/dl) severe and active infections or life expectancy less than 6 months

Other

• Large soft palate involvement \>1 cm
• Deep extension into larynx, pre-epiglottic space and deep invasion into extrinsic muscles of tongue
• Presence of severe malnutrition as defined by body mass index of below 16kg per m2 or presence of weight loss of greater than 20% in last 6 months
• Radiographic evidence of retropharyngeal and/or level VI metastasis

• Histopathology proven diagnosis of squamous cell carcinoma of the oropharynx, localized to the tonsil and/or lateralized tongue-base
• ECOG Performance Status ≤2
• Age ≥18 to 70 years
• Anesthetic fitness obtained for surgery under general anesthesia
• Resectable primary tumor with an anticipation of achieving resection free margins either by minimally invasive/open techniques
• Clinical stage III or IV, i.e. T1-T2 or T3-T4 with N0-N3. Nodal disease withextranodal extension on clinical examination/imaging may be included at the surgeon's discretion, if the nodal disease is deemed resectable by the operating surgeon
• HPV negative status determined by p16 status.
• No distant metastases below the clavicles, based upon the following minimum diagnostic workup:
  • History/physical examination by the physician.
  • Imaging of the head and neck (Contrast enhanced MRI for local workup and Chest CT/PET-CT for distant metastatic workup)
• Patients with no contraindications to Cisplatin chemotherapy and radiotherapy
• Adequate organ function
  • Hematological- Hb\> 10 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
  • Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST/ALT/ ALP ≤ 2.5 x ULN, S. albumin ≥ 30 g/L.
  • Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance \> 50 mL/min.
• Women of child bearing age should have a negative pregnancy test at the time of randomization and should be willing to use adequate contraception during the treatment phase of the trial
• Patients who can be followed up and must be able to provide informed consent prior to study entry