Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT (SALTORL)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Docetaxel; Drug: Cisplatin; Drug: Fluorouracil; Radiation: 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.

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yoann POINTREAU, Dr; Phone Number: + 33 2 43 39 13 00; Email: y.pointreau@ilcgroupe.fr
• Study Contact Backup: Name: Adeline PECHERY; Phone Number: +33 6 49 21 06 07; Email: adeline.pechery@gortec.fr

Study Locations

• France
  • Le Mans, France, 72000
    • Centre Jean Bernard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• Absence of distant metastasis, confirmed by chest TDM, abdominal ultrasound (or TDM) in case of abnormal liver function and bone scan if local symptoms.
• Absence of any participation in a clinical trial within 30 days prior to inclusion.
• Absence of any concomitant cancer treatment.
• Absence of any chronic treatment ( ≥3 months) with a daily corticosteroid dose is ≥20 mg / day of methylprednisolone or equivalent.
• Hematological function: neutrophils ≥1.5 x 109 / L, platelets ≥100 x 109 / l, hemoglobin ≥10 g / dl (or 6.2 mmol / l).
• Hepatic function: normal total bilirubin; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN (LNS) of each center; alkaline phosphatase ≤ 5 x LNS.
• Renal function: serum creatinine ≤ 120 mol / l (1.4 mg / dl); if creatinine > 120 mol / l, creatinine clearance should be ≥ 60 ml / min.
• calculated creatinine clearance (Crockcroft formula) or measured ≥ 60 ml / min
• Estimated life expectancy ≥ 3 months
• Weight loss less than 10% over the last 3 months
• Patient has given its written consent before any specific procedure of the Protocol.
• Women and men of childbearing age should have accepted a medically effective contraception during the treatment period and at least 6 months after discontinuation of study treatments (Docetaxel, 5-Fluorouracil and Cisplatin. If pregnancy is declared by a patient or partner of a patient, it must be followed to know the evolution of pregnancy.

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.
• Clinical alteration of hearing function.

• Other concomitant serious medical conditions (partial list):

  • Unstable cardiac disease despite treatment.
  • Myocardial infarction within 6 months prior to trial entry.
  • Neurological or psychiatric history such as dementia, seizures;
  • Severe uncontrolled infection.
  • Significant gastrointestinal abnormalities, including those that require parenteral nutrition, active peptic ulcer disease and a history of surgical procedures affecting absorption
  • Obstructive pulmonary disease requiring hospitalization in the year before inclusion.
  • Unstable diabetes or other cons-indications to corticosteroids.
  • Significant ophthalmologic abnormality.
  • Moderate or severe eczema.
• Allergy to iodine.
• Hypersensitivity to Docetaxel, Cisplatin or at one of their excipients.
• Concomitant use of phenytoin, carbamazepine, barbiturates and rifampicin.
• Presence, selection, psychological factors, family, social or geographical may alter patient compliance with the study protocol and follow-up, a criterion of non-inclusion. These factors should be discussed with the patient before inclusion in the trial.
• Pregnant or nursing women.
• Patient (male or female) of childbearing age not taking adequate contraceptive measures.
• Patient deprived of their liberty, without guardianship or curatorship.

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: 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.	Drug: Docetaxel; Docetaxel 75 mg / m² administered on day 1 of each cycle every 3 weeks as an intravenous (IV) infusion of one hour followed by cisplatin 75 mg / m² administered on day 1 hour infusion followed by 5-FU, 750 mg / m² / day administered in continuous infusion from D1 to D5 (or 120 hours); Other Names: Taxotere; Drug: Cisplatin; Cisplatin: 75 mg/m² for experimental arm and 100mg/m² for comparator arm administered on day 1 of each cycle every 3 weeks as an intravenous (IV) infusion.; Other Names: Cisplatine; Drug: Fluorouracil; 5-FU, 750 mg / m² / day administered in continuous infusion from D1 to D5 (or 120 hours); Other Names: 5 FU; Radiation: radiotherapy; Radiotherapy : 70Gy (2Gy/day) for 7 weeks.; Other Names: radiation therapy
Experimental: 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.	Drug: Cisplatin; Cisplatin: 75 mg/m² for experimental arm and 100mg/m² for comparator arm administered on day 1 of each cycle every 3 weeks as an intravenous (IV) infusion.; Other Names: Cisplatine; Radiation: radiotherapy; Radiotherapy : 70Gy (2Gy/day) for 7 weeks.; Other Names: radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
free survival	Minimum time between randomization and the occurrence of events such as: death, total laryngectomy, tracheotomy.	24 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	"From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months").	60 months
Progression free survival	"From date of randomization until the date of first documented progression assessed up to 60 months").	60 months
Larynx Preservation	From date of randomization up to 24 months evaluated by dynamic deglutition videoscopy	24 months after treatment initiation
Feasibility of salvage surgery	Assessing the number of recurrences that could be successfully treated with salvage surgery and description of postoperative	60 months after randomization

Collaborators and Investigators

• Sponsor: Groupe Oncologie Radiotherapie Tete et Cou
• Investigators: Principal Investigator: Yoann POINTREAU, Dr, Centre Jean Bernard

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2015
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: March 8, 2016
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Larynx, hypopharynx
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Fluorouracil
• Other Study ID Numbers: GORTEC 2014-03

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