Role of Neo-adjuvant Chemotherapy in Tongue Preservation in Locally Advanced Squamous Cell Carcinoma of Oral Tongue

Study Overview
=================
Brief Summary
-----------------
Patients enrolled for the study, who are eligible for NACT, will undergo a pre-treatment workup comprising of Evaluation Under Anesthesia (EUA) for tumor Mapping and tissue biopsy along with a PET-CT scan. Subsequently, they would undergo 3 cycles of NACT (weekly thrice) with DCF. They would be reassessed with PET-CT and EUA +/- biopsy after the end of the third cycle. Those who are achieving CR would undergo adjuvant CTRT. Subjects who have a PR in the PET-CT scan will be re-classified based on the biopsy report. If they remain in the PR group they will undergo surgery but if the biopsy in is negative for malignancy, they will undergo adjuvant CTRT. Those subjects with SD or PD would undergo surgery. Subsequently, further radiation and/ or chemotherapy will be decided based on the final histopathology (of the surgical specimen) reports. PET-CT and EUA +/- HPE analyses would be repeated on follow-up after 3 months of treatment completion.

Detailed Description
-----------------
Patients enrolled for the study, who are eligible for Neoadjuvant chemotherapy, will undergo a pre-treatment workup comprising of Evaluation Under Anesthesia (EUA) for tumor Mapping and tissue biopsy along with a PET-CT scan. Subsequently, they would undergo 3 cycles of Neoadjuvant chemotherapy (weekly thrice) with injection Docetaxel, Cisplatin, and 5-FU. They would be reassessed with PET-CT and EUA +/- biopsy after the end of the third cycle. Those who are achieving a Complete Response (CR) would undergo adjuvant chemo-radiotherapy. Subjects who have a partial response (PR) in the PET-CT scan will be re-classified based on the biopsy report. If they remain in the PR group they will undergo surgery. If the biopsy in these patients is negative for malignancy, they will undergo adjuvant chemoradiotherapy. Those subjects with stable disease (SD) or progressive disease (PD) would undergo surgery. Subsequently, further radiation and/ or chemotherapy will be decided based on the final histopathology (of the surgical specimen) reports. PET-CT and EUA +/- HPE analyses would be repeated on follow-up after 3 months of treatment completion.

Official Title
-----------------
Role of Neo-adjuvant Chemotherapy in Organ Preservation in Locally Advanced Squamous Cell Carcinoma of Oral Tongue

Conditions
-----------------
Tongue Neoplasms, Squamous Cell Carcinoma, Anterior Tongue Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Docetaxel
* Drug: Cisplatin
* Drug: 5FU
* Radiation: Radiotherapy
* Procedure: Glossectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of newly diagnosed squamous cell carcinoma (well/ moderately/ poorly differentiated) of oral tongue (anterior two third) presenting to Health Care Global Enterprises Ltd between January 2016 to March 2017 will be included in the study. Stage III and stage IV (T3, 4 N0-3, M 0) and selected cases of T2 with advanced nodal status will also be included in the study. Exclusion Criteria: Patients having recurrence/ residual disease of oral tongue. Patients who have received alternative treatments before being evaluated for NACT Patient who are not fit for NACT Patient not able to give consent

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant Arm<br>Study Subjects, eligible for NACT would undergo a pretreatment workup with Evaluation Under Anesthesia for tumor Mapping and tissue biopsy along with a PET-CT scan. They would undergo 3 cycles of NACT (weekly thrice) with injection Docetaxel, Cisplatin and 5-FU after which reassessment with PET-CT and EUA +/- biopsy would be done. Those achieving CR would undergo adjuvant CTRT while subjects with PR in PET-CT scan will be reclassified based on the biopsy report. If biopsy is negative for malignancy, they will undergo adjuvant CTRT but would undergo surgery if in the PR group. Subjects with SD or PD would undergo surgery. PET-CT and EUA +/- HPE analyses would be repeated on follow-up after 3 months of treatment completion. | Drug: Docetaxel<br>* Neoadjuvant Arm<br>Drug: Cisplatin<br>* Neoadjuvant Arm<br>Drug: 5FU<br>* Neoadjuvant Arm<br>Radiation: Radiotherapy<br>* Neoadjuvant Arm<br>Procedure: Glossectomy<br>* Neoadjuvant Arm<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tongue Preservation Rate | A ratio of the number of study subjects who have achieved a complete response and do not require surgery, after 3 cycles of NaCT to the total number of subjects recruited to the study. | At Response evaluation post 3rd CT Cycle (approximately 7 months post recruitment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival Rate (Date of diagnosis to date of death or last follow-up) in different sub-cohorts of the study | 2 years post treatment completion | 
| Progression Free Survival | Progression Free Survival Rate (Primary treatment end date to date of progression or last follow-up) in difference sub-cohorts of the study | 2 years post treatment completion | 
| Sensitivity and Specificity of PET-CT | Ability of PETCT (along with HPE and EUA) to detect response rates in study subjects undergoing NACT for Ca Tongue | At Baseline and after 12-15 weeks (post 3 cycles of NaCT (Typically 3 weeks)) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neoadjuvant Chemotherapy, Tongue Malignancy, Squamous Cell Carcinoma