SALTORL: Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 Design
Arms and Interventions
| 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:
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:
Drug: Fluorouracil
5-FU, 750 mg / m² / day administered in continuous infusion from D1 to D5 (or 120 hours)
Other Names:
Radiation: radiotherapy
Radiotherapy : 70Gy (2Gy/day) for 7 weeks.
Other Names:
|
| 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:
Radiation: radiotherapy
Radiotherapy : 70Gy (2Gy/day) for 7 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- free survival [24 months after treatment initiation]
Minimum time between randomization and the occurrence of events such as: death, total laryngectomy, tracheotomy.
Secondary Outcome Measures
- Overall survival [60 months]
"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").
- Progression free survival [60 months]
"From date of randomization until the date of first documented progression assessed up to 60 months").
- Larynx Preservation [24 months after treatment initiation]
From date of randomization up to 24 months evaluated by dynamic deglutition videoscopy
- Feasibility of salvage surgery [60 months after randomization]
Assessing the number of recurrences that could be successfully treated with salvage surgery and description of postoperative
Eligibility Criteria
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,
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T3 without massive infiltration by endolarynx transglottic injury,
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N0 to N2c
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No distant metastasis
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No associated cancer or earlier
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Patients Previously Untreated
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Age> 18 years and <75 years
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PS 0 or 1 according to WHO
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Tumor volume assessable by RECIST.
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Absence of distant metastasis, confirmed by chest TDM, abdominal ultrasound (or TDM) in case of abnormal liver function and bone scan if local symptoms.
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Absence of any participation in a clinical trial within 30 days prior to inclusion.
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Absence of any concomitant cancer treatment.
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Absence of any chronic treatment ( ≥3 months) with a daily corticosteroid dose is ≥20 mg / day of methylprednisolone or equivalent.
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Hematological function: neutrophils ≥1.5 x 109 / L, platelets ≥100 x 109 / l, hemoglobin ≥10 g / dl (or 6.2 mmol / l).
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Hepatic function: normal total bilirubin; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN (LNS) of each center; alkaline phosphatase ≤ 5 x LNS.
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Renal function: serum creatinine ≤ 120 mol / l (1.4 mg / dl); if creatinine > 120 mol / l, creatinine clearance should be ≥ 60 ml / min.
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calculated creatinine clearance (Crockcroft formula) or measured ≥ 60 ml / min
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Estimated life expectancy ≥ 3 months
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Weight loss less than 10% over the last 3 months
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Patient has given its written consent before any specific procedure of the Protocol.
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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
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tumor requiring the completion of an immediately tracheotomy.
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Tumour available immediately to partial surgery.
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tumor requiring circular hypopharyngectomie
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N3 nodal injury
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Vaccination against yellow fever recent or anticipated
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Deficit known dihydropyrimidine dehydrogenase (DPD)
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Other malignancies within 5 years prior to randomization, with the exception of adequately treated basal skin cancer and carcinoma in situ of the cervix.
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Patients with AST or ALT> 1.5xULN associated with alkaline phosphatase > 2.5x LNS will not be eligible for testing.
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symptomatic neuropathy grade ≥2 with NCI-CTC.
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Clinical alteration of hearing function.
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Other concomitant serious medical conditions (partial list):
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Unstable cardiac disease despite treatment.
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Myocardial infarction within 6 months prior to trial entry.
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Neurological or psychiatric history such as dementia, seizures;
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Severe uncontrolled infection.
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Significant gastrointestinal abnormalities, including those that require parenteral nutrition, active peptic ulcer disease and a history of surgical procedures affecting absorption
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Obstructive pulmonary disease requiring hospitalization in the year before inclusion.
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Unstable diabetes or other cons-indications to corticosteroids.
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Significant ophthalmologic abnormality.
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Moderate or severe eczema.
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Allergy to iodine.
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Hypersensitivity to Docetaxel, Cisplatin or at one of their excipients.
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Concomitant use of phenytoin, carbamazepine, barbiturates and rifampicin.
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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.
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Pregnant or nursing women.
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Patient (male or female) of childbearing age not taking adequate contraceptive measures.
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Patient deprived of their liberty, without guardianship or curatorship.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hôpital Bretonneau, Service CORad Pôle Henry S Kaplan | Tours | France | 37044 |
Sponsors and Collaborators
- Groupe Oncologie Radiotherapie Tete et Cou
Investigators
- Principal Investigator: Gilles CALAIS, Hôpital Bretonneau, Service CORad Pôle Henry S Kaplan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GORTEC 2014-03