Clinical trial NCT03340896: Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Larynx, hypopharynx
Lead sponsor: Groupe Oncologie Radiotherapie Tete et Cou
Sponsor class: OTHER
First posted: 2017-11-14
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
* 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.

Primary outcomes:
measure: free survival
timeFrame: 24 months after treatment initiation
Secondary outcomes:
measure: Overall survival
timeFrame: 60 months
measure: Progression free survival
timeFrame: 60 months
measure: Larynx Preservation
timeFrame: 24 months after treatment initiation
measure: Feasibility of salvage surgery
timeFrame: 60 months after randomization
Other outcomes:
Locations:
city: Le Mans
country: France
facility: Centre Jean Bernard
Study officials:
affiliation: Centre Jean Bernard
name: Yoann POINTREAU, Dr
role: PRINCIPAL_INVESTIGATOR
References: