Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers: (SurVIC)

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

A majority of oral cancer patients 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 not well defined in curative setting apart from 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).

Earlier studies suffered from their heterogeneous patient population- all head and neck subsites together and included a spectrum ranging from early- stage operable cases to inoperable cancer. 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

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. taking 10% of withdrawal of consent, a total of 346 patients need to be included.

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 or TPX 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 Overview

• Status: Recruiting
• Conditions: Head and Neck Neoplasms; Oral Cancer
• Intervention / Treatment: Combination product: Surgery and Adjuvant Treatment; Combination product: TPF or TPX Regimen (2# ICT) --> Surgery and Adjuvant Treatment

• Study Type: Interventional
• Enrollment (Estimated): 346
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dharma R Poonia, MS DNB; Phone Number: 9958654196; Email: pooniadr@aiimsjodhpur.edu.in

Study Locations

• India
  • Bathinda, India
    • Not yet recruiting
    • All India Institute of Medical Sciences, Bathinda
    • Contact: Rohit Mahajan
  • Dehradun, India
    • Not yet recruiting
    • Shri Mahant Indresh Hospital, Dehradun
    • Contact: Pankaj K Garg
  • Lucknow, India
    • Not yet recruiting
    • King George's Medical University
    • Contact: Vijay Kumar
  • Rishīkesh, India
    • Not yet recruiting
    • All India Institute of Medical Sciences, Rishikesh
    • Contact: Amit Sehrawat
  • Udaipur, India
    • Not yet recruiting
    • Geetanjali Medical College, Udaipur
    • Contact: Ashish Jhakhetiya
  • Orisa
    • Bhubaneshwar, Orisa, India, 751019
      • Not yet recruiting
      • All India Institute of Medical Sciences, Bhubaneshwar
      • Contact: Dillip Mudully
  • Rajasthan
    • Jodhpur, Rajasthan, India, 342005
      • Recruiting
      • All India Institute of Medical Sciences, Jodhpur
      • Contact: Dharma R Poonia, MS DNB
      • Principal Investigator: Dharma R Poonia, MS DNB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed, treatment naïve, biopsy or cytology proven OSCC
• Clinical Stage cT1-4a, cN2-N3**, M0- as per UICC 2018
• No evidence of distant metastases on chest x-ray and/or CT Thorax
• ECOG PS 0-2
• No contraindication to Cisplatin or radiotherapy***
• Patients eligible for definitive curative intent treatment after discussion in multidisciplinary tumour board
• Adequate organ function at time of participation, defined as Haematological: Haemoglobin > 9gm/dl, ANC ≥ 1500/cmm3, Platelet ≥100000/cmm3 Liver Function test: Bilirubin ≤2 x upper limit normal (ULN), AST/ALT/ ALP ≤ 2.5 x ULN Renal Function test: Creatinine ≤ 1.5 ULN, Creatinine Clearance ≥60 ml/min.

Exclusion Criteria:

• Pregnant
• History of moderate to severe hearing loss.
• History of previous malignancy excluding non-melanoma skin cancers or cervical carcinoma in situ.
• Documented Weight loss of more than 15% in the last 6 months.
• Patients with known HIV, hepatitis B or C infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surg Arm; Wide Local Excision (WLE) with Comprehensive neck dissection Adjuvant Treatment as per current standard Guidelines	Combination product: Surgery and Adjuvant Treatment; Wide Local Excision (WLE) with Comprehensive neck dissection and Adjuvant Treatment as per current standard Guidelines.
Experimental: ICT Arm; 2# of Chemotherapy before the Stadrard Surery: Either TPF or TPX Wide Local Excision (WLE) with Comprehensive neck dissection Adjuvant Treatment as per current standard Guidelines	Combination product: TPF or TPX Regimen (2# ICT) --> Surgery and Adjuvant Treatment; TPF: IINJ DOCETAXEL 75mg/M2 in 500 ML NORMAL SALINE(PVC free container/glass bottle) via codon filter OVER 60 MIN (DAY 1 ONLY) INJ. CISPLATIN 75 MG/M 2 IN 500 ML NS IV OVER 1 HOUR ON DAY1 ONLY INJ. 5FU 750 MG/M2 IV THROUGH INFUSION PUMP OVER 24 HOURS D 1-4 Or TPX Regimen INJ DOCETAXEL 75mg/M2 in 500 ML NORMAL SALINE(PVC free container/glass bottle) via codon filter OVER 60 MIN (DAY 1 ONLY) INJ. CISPLATIN 75 MG/M 2 IN 500 ML NS IV OVER 1 HOUR ON D1 ONLY TAB. CAPECITABINE 850-1000MG/M2 TWICE A DAY 30 MINUTES AFTER MEALS FOR 14 DAYS IN A THREE WEEKLY CYCLE Surgery and Adjuvant Treatment Patients with PR/CR or SD will go for surgical resection. Patients having PD but still localized and resectable will be offered surgical resection, other would undergo radical CTRT or Palliative Treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Date of randomization to the date of clinical or pathological evidence of recurrence	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Date of randomization to the date of death due to any reason.	2 Years
Treatment Completion Rate	Number of Participants completing the treatment	2 Years
Treatment Related Toxicity	Chemotherapy Related and Radiotherapy Related: Common Terminology Criteria for Adverse Events (CTCAE v5.0)	2 Years
Quality of Life using PROs	FACT HN Scale	3 Months; 6 Months; 12 Months; 18 Months; 24 Months; 36 Months; 48 Months; 60 Months
Postoperative Surgical Morbidity	Clavien Dindo Scale	30 Days and 90 Days
Biobanking of Tumor, Non Tumor tissue and Blood	DNA Sequencing using NGS to assess the genetic alterations	2 Years
Financial Toxicity using Questionnaire	FACT Scale	3 Months; 6 Months; 12 Months; 18 Months; 24 Months; 36 Months; 48 Months; 60 Months
Early Radiotherapy Related Toxicity	RTOG Criteria	30 Days
Late Radiotherapy Relate Toxicity	RTOG Criteria	2 Years

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, Jodhpur
• Collaborators: King George's Medical University; All India Institute of Medical Sciences, Bhubaneswar; All India Institute of Medical Sciences, Rishikesh; All India Institute of Medical Sciences, Bathinda; Shri Mahant Indiresh Hospital, Dehradun; Geetanjali Medical College, Udaipur
• Investigators: Principal Investigator: Dharma R Poonia, MS DNB, AIIMS Jodhpur

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: October 7, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 2, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Mouth Neoplasms
• Other Study ID Numbers: 2023/5784

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No