Randomised trial comparing Upfront surgery versus chemoradiotherapy (CCRT) in Head and Neck squamous cell carcinoma of unknown primary with neck node metastasis:

Phase 3

Conditions: Health Condition 1: C801- Malignant (primary) neoplasm, unspecifiedHealth Condition 2: C760- Malignant neoplasm of head, face and neck

Recruitment & Eligibility

Inclusion Criteria

1. Head Neck Cancer of Unknown Primary (HNCUP), as defined by AJCC 8th edition.

2. Squamous cell carcinoma only.

3. Karnofsky performance status >=70 and adequate hematologic, renal, and hepatic function.

4. Patients consenting to participate in the study.

Exclusion Criteria

1. Lymph node (core) biopsy positive patients for HPV (p16-IHC) and EBV (EBV-ISH) and

2. Isolated Level IV metastasis in a case of HNCUP

3. Prior chemotherapy or radiation therapy to the head and neck region.

4. Evidence of distant metastasis.

5. Prior malignancy within the previous 5 years, other than curatively treated skin cancer or cervical intraepithelial neoplasia.

5. Pregnant and lactating women.

6. Unresectable nodal disease

7. Exclusion criteria for cisplatin, i.e.

â?? The presence of moderate to severe sensorineural hearing loss.

â?? The presence of renal dysfunction, i.e. creatinine clearance < 50 cc/min

â?? The presence of inadequate bone marrow reserve, as defined as Hb < 9 g/dl, absolute neutrophil count < 1.5 x 109/L, platelet count < 100 x 109/L

â?? The presence of hepatic dysfunction, i.e. bilirubin >= 2 x upper limit normal (ULN), AST/ALT/ALP >= 2.5 xULN, S. albumin < 30 g/L.

8. Serious co-morbidities such as severe cardiac failure or severe pulmonary compromise or severe and active infections.

Primary Outcome Measures

Name	Time	Method
To test whether upfront surgery followed by adjuvant treatment offers better overall survival in comparison to chemoradiotherapy followed by salvage neck dissection for residual disease. <br/ ><br> <br/ ><br>Timepoint: at 3-6 months <br/ ><br> <br/ ><br>

Secondary Outcome Measures

Name	Time	Method
1. Disease-free survival (DFS) <br/ ><br>2. Loco-regional control (disease progression/recurrent or new disease /death due to any cause) <br/ ><br>3. Treatment-related toxicity (CTCAE/Clavin-Dindo Classification) <br/ ><br>4. QoL (EORTC-QLQ-30, HN-35) <br/ ><br>Timepoint: 1. Patient will be assessed during routine treatment. <br/ ><br>2. After treatment completion patient will be clinically evaluated after 6 weeks <br/ ><br> & will undergo response assesment scan (PET-CT/CECT scan) at 10-12 weeks. <br/ ><br>3.Further evaluation will be based on any clinical or radiological suspicion. <br/ ><br>4.All enrolled patients will be followed up for at least 3 years.