Title

Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cavity Squamous Cell Cancers With Advanced Nodal Disease (SurVIC Trial): A Phase 3 Multicentric Randomized Controlled Trial

Rationale and Knowledge gap

Majority of oral cancers in India present in the advanced stage hence tend to have poor oncological outcomes. Chemotherapy has been associated with improved oncological outcomes in various cancers, but its role in oral cancer is still not well defined in curative settings, beyond radio sensitization. Attempted trials of Neoadjuvant chemotherapy failed to show oncological advantage despite an excellent response rate, in part due to poor patient selection. Patients with a biologically aggressive disease are more likely to benefit, hence we intend to find out the oncological advantage of adding induction chemotherapy to oral squamous cell cancer with advanced nodal disease (N2-N3).

Novelty

Earlier studies suffered from their heterogeneous patient population- all head and neck subsites together and included either inoperable cancer/ early-stage operable cases. Due to such patient selection, the intended results were never met. The current study is intended to study the role of chemotherapy in curable patients who are most likely to benefit (biologically aggressive and advanced stage of presentation).

Objective

Primary: 

●      To study the 2 year disease free survival by adding induction chemotherapy before surgery in patients of oral cancer with advanced nodal disease as compared to upfront surgery. 

Secondary: 

●      To assess treatment related outcomes between the treatment arms- Response rate; Treatment compliance;  treatment related toxicity, postoperative complications and Quality of life. 

●      To study the overall survival at 2 years. 

●      Oral cancer tissue biobanking for future translational research.  

Study population

Operable Oral cavity Squamous cell carcinoma with advanced nodal disease (N2-N3)

Study Design

Open label, Multi centric, randomized controlled trial with allocation ratio of 1:1

Study

Sites

Leading Center: AIIMS Jodhpur

Collaborating Centers:

1.     AIIMS Bhubaneswar

2.     AIIMS Rishikesh

3.     AIIMS Bathinda

4.     King’s George Medical university Lucknow

5.     Shri Mahant Indiresh Hospital, Dehradun

6.     Geetanjali Medical College, Udaipur

Sample Size

The primary end point is disease-free survival. In order to have 80% power to detect a hazard ratio of 0.67, using a two-sided significance level, a total of 184 events are needed. Assuming an accrual rate of 15 patients a month, 300 patients need to be recruited. The analysis of DFS will take place 32 months after the start of the trial. The follow-up of patients will continue for 5 years. The analysis of OS will be conducted when 184 deaths are observed.

Inclusion Criteria

Biopsy proven, operable oral Squamous cell carcinoma cT1-T4; cN2-N3, with adequate organ function, Age- 18-75 years, ECOG-PS:0-2

Treatment Arms

Standard Arm (SURG arm):

Surgery (Wide local Excision/composite resection with neck dissection) followed by adjuvant Radiotherapy ± Concurrent Chemotherapy

Experimental Arm (ICT):

2# TPF based induction chemotherapy followed by Surgery (Wide local Excision/composite resection with neck dissection) followed by adjuvant Radiotherapy ± Concurrent Chemotherapy

Study endpoints

Primary- Disease free survival

Secondary- Overall survival/ Quality of life/ Toxicity of treatment/ Treatment tolerance

Study duration

1.     Preparation/ site initiation/IEC clearances/ MOUs- 3 Months

2.     Participants accrual- 24 Months

3.     Follow up and trial completion report-  9 Months

4.     Follow up for Overall survival- 24 Months

Feasibility

As per past institutional experience, we expect to enrol the desired number of cases in 2 years. The approximate number of case accrual per centre is as follows-

●      AIIMS Jodhpur- 50/ year

●      King’s George Medical university Lucknow- 40 patients/ year

●      AIIMS Bhubaneswar- 25 patients/ year

●      AIIMS Rishikesh- 25 patients/ year

●      AIIMS Bathinda- 20 patients/ year

●      Shri Guru Ram Rai Institute of medical and Health Sciences & Shri Mahant Indiresh Hospital, Dehradun- 20 patients/ year

●      Geetanjali Medical College, Udaipur- 20 patients/ year