Phase III Trial of Laryngeal Preservation Comparing Induction Chemotherapy With Cisplatin, 5-fluorouracil and Docetaxel (TPF) Followed by Radiotherapy and Concomitant Administration of Radiotherapy With Cisplatin
Overview
- Phase
- Phase 3
- Intervention
- Docetaxel
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Sponsor
- Groupe Oncologie Radiotherapie Tete et Cou
- Enrollment
- 256
- Locations
- 1
- Primary Endpoint
- free survival
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This study compare the survival without laryngeal dysfunction 2 years after the end of treatment, obtained by chemotherapy followed by radiotherapy or chemotherapy with cisplatin administrated during radiotherapy.
Detailed Description
In patients with tumors classified as T3 or T4 larynx and hypopharynx, the usually recommended treatment was total laryngectomy.This intervention allows to obtain locoregional disease control in 75% of cases, without laryngectomy TPF arm followed by radiotherapy was validated in a Phase III (GORTEC 2000-01), it will be the standard treatment. The RTOG study concluded that chemotherapy administrated during radiotherapy became a standard of laryngeal preservation. Taking together all these considerations, it is necessary to perform a direct comparison in a randomized trial to further test this hypothesis. Chemotherapy followed by radiotherapy will be the standard arm. It hopes to increase the survival rate from 52% to 65% in the experimental arm.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Squamous cell carcinoma of the larynx or hypopharynx, histologically proven, locally advanced:
- •T2 not accessible to a supra-cricoid partial laryngectomy or not,
- •T3 without massive infiltration by endolarynx transglottic injury,
- •N0 to N2c
- •No distant metastasis
- •No associated cancer or earlier
- •Patients Previously Untreated
- •Age\> 18 years and \<75 years
- •PS 0 or 1 according to WHO
- •Tumor volume assessable by RECIST.
Exclusion Criteria
- •transglottic T3 with massive infiltration of hemilarynx or T4 with massive cartilaginous tumor lysis or reverse cricoarythénoïdenne region or posterior hypopharyngeal wall
- •tumor requiring the completion of an immediately tracheotomy.
- •Tumour available immediately to partial surgery.
- •tumor requiring circular hypopharyngectomie
- •N3 nodal injury
- •Vaccination against yellow fever recent or anticipated
- •Deficit known dihydropyrimidine dehydrogenase (DPD)
- •Other malignancies within 5 years prior to randomization, with the exception of adequately treated basal skin cancer and carcinoma in situ of the cervix.
- •Patients with AST or ALT\> 1.5xULN associated with alkaline phosphatase \> 2.5x LNS will not be eligible for testing.
- •symptomatic neuropathy grade ≥2 with NCI-CTC.
Arms & Interventions
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
Intervention: Docetaxel
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
Intervention: Cisplatin
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
Intervention: Fluorouracil
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
Intervention: radiotherapy
Cisplatin and radiotherapy
Drug and radiation • Cisplatin: 100 mg / m² administered IV at J1, J22 and J43 of radiotherapy . Radiotherapy 70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
Intervention: Cisplatin
Cisplatin and radiotherapy
Drug and radiation • Cisplatin: 100 mg / m² administered IV at J1, J22 and J43 of radiotherapy . Radiotherapy 70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
Intervention: radiotherapy
Outcomes
Primary Outcomes
free survival
Time Frame: 24 months after treatment initiation
Minimum time between randomization and the occurrence of events such as: death, total laryngectomy, tracheotomy.
Secondary Outcomes
- Overall survival(60 months)
- Progression free survival(60 months)
- Larynx Preservation(24 months after treatment initiation)
- Feasibility of salvage surgery(60 months after randomization)