Phase III Trial of Surgery Followed by Conventional RT(5fr/Week)Vs.Concurrent Chemo-Radiotherapy Vs.Accelerated RT(6fr/Week)in High Risk, Loco-Regionally Advanced, Stage III&IVA, Resectable, Squamous Cell Carcinomas of Oralcavity
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Tata Memorial Hospital
- Enrollment
- 900
- Locations
- 2
- Primary Endpoint
- Local-regional failure
Study Overview
Brief Summary
To demonstrate whether addition of Concurrent chemotherapy to post-operative adjuvant radiotherapy OR shortening of duration of post-operative radiotherapy, by administering 6 fractions / week instead of 5 fractions / week improves local-regional control and / or overall survival in high risk, locally advanced, resectable, squamous cell carcinoma of oral cavity.
Detailed Description
Locally advanced, stage III and IVA, resectable, squamous cell carcinomas of oral cavity are conventionally treated with surgery, followed by post-operative radiotherapy. Local-regional recurrence remains the most frequent cause of failure of this treatment. The results of conventional therapy are dismal with five-year survival of less than 30% and 60-80% incidence of local-regional failure within 3 years. There are various known histological prognostic factors. The local-regional control and overall survival are extremely poor in high risk patients with these poor prognostic factors. In an attempt to improve the outcome of this high risk group, various alternative treatment policies such as addition of chemotherapy to radiotherapy or altered fractionation schedules have been tried. But till date, there is no alternative treatment modality with acceptable toxicity, available for these patients.
Aims Of Study: To demonstrate whether addition of Concurrent chemotherapy to post-operative adjuvant radiotherapy OR shortening of duration of post-operative radiotherapy, by administering 6 fractions / week instead of 5 fractions / week improves local-regional control and / or overall survival in high risk, locally advanced, resectable, squamous cell carcinoma of oral cavity.
Eligibility criteria: Locally advanced, stage III and IVA, resectable, squamous cell carcinomas of oral cavity with one of the following poor prognostic factors extracapsular nodal extension, involvement of > 2 regional lymph nodes, margin of resection with invasive cancer Extensive soft tissue and / or skin infiltration requiring major reconstructive procedure.
Peri-neural invasion with positive lymph node. Lympho-vascular embolisation with positive lymph node.
Trial Design The eligible patients will be randomly allocated to one of the three arms
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Previously untreated, resectable, loco-regionally advanced, stage III & IV, biopsy-proven squamous cell carcinoma of the oral cavity. (Clinically lower stage patients will also be included if upstaged to pathological stage III or IV after Surgery)
- •One or more of the following must be present:
- •extracapsular nodal extension, involvement of > 2 regional lymph nodes, margin of resection with invasive cancer (on histopathology) Extensive soft tissue and / or skin infiltration requiring major reconstructive procedure.
- •Peri-neural invasion with positive lymph node(s). Lymphovascular embolisation with positive lymph node(s). Age >
- •Karnofsky performance status of >
- •WBC > 3500, platelets > 100,000 Serum creatinine < 1.2 mg / m2 Signed study-specific informed consent form. Protocol treatment must begin within 8 weeks surgery.
Exclusion Criteria
- •Gross (visible or palpable) residual disease left after surgery. Prior chemotherapy or radiation therapy to the head and neck region.
- •Evidence of distant metastasis. Any post-operative complication which will delay starting of adjuvant treatment for more than 8 weeks.
- •Presence of synchronous or concurrent head and neck primary tumors. Prior malignancy within the previous 5 years. Patients who because of their medical status are not candidates for the proposed treatment.
- •Age > 65 years. Poor expected follow up.
Outcomes
Primary Outcomes
Local-regional failure
Secondary Outcomes
- Overall survival
- Treatment related toxicity
- Protocol compliance
- Overall treatment time
- Quality of life: assessment by EORTC-QLQ-C30 and EORTC-H&N-35