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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 346
- 试验地点
- 9
- 主要终点
- Disease Free Survival
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Disease Free Survival
时间窗: 2 Years
Date of randomization to the date of clinical or pathological evidence of recurrence
次要结局
- Overall Survival(2 Years)
- Treatment Completion Rate(2 Years)
- Treatment Related Toxicity(2 Years)
- Quality of Life using PROs(3 Months; 6 Months; 12 Months; 18 Months; 24 Months; 36 Months; 48 Months; 60 Months)
- Postoperative Surgical Morbidity(30 Days and 90 Days)
- Biobanking of Tumor, Non Tumor tissue and Blood(2 Years)
- Financial Toxicity using Questionnaire(3 Months; 6 Months; 12 Months; 18 Months; 24 Months; 36 Months; 48 Months; 60 Months)
- Early Radiotherapy Related Toxicity(30 Days)
- Late Radiotherapy Relate Toxicity(2 Years)
研究者
Dharma Ram Poonia
Principal Investigator & Associate Professor Surgical Oncology
All India Institute of Medical Sciences, Jodhpur