Evaluation of Lymphocyte-Sparing Radiotherapy and All-Trans Retinoic Acid in Lateralized Oropharyngeal, Laryngeal, and Hypopharyngeal Squamous Cell Carcinoma

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What is this study about?

This clinical trial is focused on studying treatments for a type of cancer known as squamous cell carcinoma that affects the head and neck area, specifically the oropharynx, larynx, and hypopharynx. The study will explore the effects of a medication called all-trans retinoic acid (ATRA), also known by its brand name Vesanoid, in combination with different approaches to radiotherapy, which is a treatment that uses high-energy rays to target and kill cancer cells.

The purpose of the study is to assess how effective ATRA and tailored radiotherapy are in treating patients with localized squamous cell carcinoma of the head and neck. Participants in the study will receive either standard or reduced-target volume radiotherapy, with or without ATRA. The study will also involve the use of other medications, including cetuximab and cisplatin, which are commonly used in cancer treatment. Cetuximab is a protein-based medication, while cisplatin is a chemical compound used to stop the growth of cancer cells.

Throughout the study, participants will receive treatments over a period of time and will be monitored for their response to the therapy. The study aims to understand the impact of these treatments on the survival and quality of life of patients, as well as any potential side effects. The ultimate goal is to improve treatment strategies for head and neck cancer, providing better outcomes for patients.

1 study treatment starts

after you join the study, treatment begins as part of a randomised trial. randomised means that assignment to a study group is made by chance.

the study compares standard radiotherapy with reduced-target radiotherapy, with or without atRA (all-trans retinoic acid, also called tretinoin).

2 tretinoin by mouth, if assigned

if you are assigned to receive it, you take tretinoin by mouth at a dose of 150 mg/m2.

it is taken once daily for 2 weeks.

3 radiotherapy during the study

you receive radiotherapy, which means treatment with radiation.

the study uses either standard radiotherapy or reduced-target radiotherapy, depending on the group to which you are assigned.

4 background medicine given by vein

some patients also receive study background medicines by intravenous infusion, which means through a vein.

cisplatin is given at a dose of 40 mg/m2 intravenously.

cetuximab is given at a dose of 400 mg/m2 intravenously.

5 follow-up after treatment

after (chemo)-radiotherapy ends, some patients have a neck node dissection about 4 months later if they are going to have this procedure.

a neck node dissection means removal of lymph nodes in the neck.

6 study assessment during and after the trial

the study checks for event-free survival (EFS), which means the length of time without a study-defined cancer-related event.

the study also assesses return of disease in the local area, in the regional area, and spread to distant sites.

it records side effects using a standard grading system called NCI CTCAE 5.0, which is a list used to describe how severe side effects are.

it measures changes in quality of life, fatigue, swallowing, and pain using questionnaires.

it also includes immunomonitoring, which means checking immune cells in blood samples.

Who Can Join the Study?

Adults only: the patient must be 18 years old or older when signing the informed consent form, which is the written permission to join the study.
The patient must have a previously untreated primary tumor in the head and neck area, with a histologically confirmed diagnosis, meaning the cancer has been proven by a tissue sample, of squamous cell carcinoma in the oropharynx (throat area behind the mouth), larynx (voice box), or hypopharynx (lower part of the throat).
The tumor must be localized up to, but not crossing, the midline, meaning it must stay on one side and not extend across the center line of the throat.
For oropharynx p16-, the cancer stage must be T1 N2a-N2b, T2 N0-N2b, or T3 N0-N2b according to UICC 8th edition, which is a standard cancer staging system.
For oropharynx p16+, the cancer stage must be T1 N1 with multiple lymph nodes, or T2-T3 N0-N1 according to UICC 8th edition.
The patient must have had lymph node staging checked by FDG-PET/CT, which is a special scan that looks for cancer activity, and there must be no cancer uptake on the opposite side of the neck.
The patient must be able to receive radiotherapy (RT), which is treatment with radiation, or concurrent chemoradiotherapy, which means radiation given together with chemotherapy, as judged by the treating doctor based on the tumor stage, tumor location, and the patient’s condition.
The patient must have an ECOG performance status of 0 or 1, meaning they are fully active or only slightly limited in normal daily activities.
The patient must have adequate blood, liver, and kidney function based on lab tests done within 7 days before randomization (the time when the study treatment is assigned). This means: neutrophils (a type of white blood cell that fights infection) must be above 1.5 x 10^9/L; platelets (cells that help blood clot) must be above 75 x 10^9/L; white blood cells must be at least 3.0 x 10^9/L; total bilirubin (a liver test) must be less than 1.5 times the upper normal limit, except in Gilbert’s syndrome, where up to 3 times the upper normal limit is allowed; ALT and AST (liver enzymes) must be no more than 2.5 times the upper normal limit; albumin (a blood protein that reflects liver and nutrition status) must be above 3.0 g/dL; and serum creatinine (a kidney test) must be less than 1.5 times the upper normal limit.
The patient must have a QTcF of 450 ms or less for men and 470 ms or less for women on screening electrocardiograms, which are heart tracing tests, based on 3 ECGs done within 7 days before randomization.
Women who can become pregnant must have a negative pregnancy test in blood or urine within 7 days before randomization and must agree to use effective contraception, meaning reliable birth control, during the study and for up to 1 month after treatment ends.
Men who can father a child must agree to use effective contraception during the study and for up to 1 month after treatment ends.
The patient must understand the study, must sign and date the informed consent form before any study-specific procedures, and must be willing and able to follow the study visits and procedures.
The patient must have medical insurance in the country where this is required.

Who Cannot Join the Study?

People whose main tumor crosses the middle line of the body, or who have tumors on both sides, cannot take part.
People with certain very early or advanced lymph node patterns cannot take part, including T1-N0 or T1-N1 with p16-negative, T1-N0 with p16-positive, T4 with either p16-negative or p16-positive, both-sided lymph nodes, or lymph node disease larger than 6 cm (about 2.4 inches).
People whose main tumor size is unknown, with T0-N1 to T0-N3 disease, cannot take part.
People with cancer activity on the side opposite the main tumor on a FDG-PET/CT scan cannot take part. This scan is an imaging test that shows areas with high sugar use, which can suggest cancer activity.
People who had any previous anti-cancer treatment for this head and neck cancer cannot take part, including chemotherapy (anti-cancer drugs), radiotherapy (treatment with radiation), targeted therapy, immunotherapy (treatment that affects the immune system), or any other approved or experimental cancer treatment.
People who had another cancer within the last 3 years cannot take part, except for treated carcinoma in situ of the cervix (very early cancer in the neck of the womb), basal cell or squamous cell skin cancer, or localized prostate cancer treated with surgery aiming to cure it.
People who need, or are expected to need, immunosuppressive medicine cannot take part. These are medicines that reduce the body’s immune response, such as glucocorticoids, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, or anti-TNF-alpha agents. Small exceptions are made for nasal, inhaled, or skin steroids, or low-dose steroids up to 10 mg/day of prednisone or an equal dose.
People who need, or are expected to need, immunostimulatory agents cannot take part. These are medicines that increase immune activity, such as interferons and IL-2 (interleukin-2).
People who are receiving any other cancer treatment, either approved or experimental, or who are taking part in another clinical trial with treatment goals, cannot take part.
People with a serious infection in the 4 weeks before randomization cannot take part, including cases that needed hospital care for infection problems, infection in the blood (bacteremia), or severe pneumonia.
People with active hepatitis B cannot take part. This means a positive HBsAg test at screening.
People with active hepatitis C cannot take part. People with hepatitis C antibodies are allowed only if a PCR test shows no HCV RNA in the blood at screening.
People with HIV infection cannot take part.
People with active tuberculosis cannot take part.
People with psychological, memory, family, social, or travel problems that may make it hard to follow the study plan, complete questionnaires, or attend follow-up visits cannot take part.
People with a known allergy or strong reaction to tretinoin, other retinoids (vitamin A-like medicines), soya, peanut, or any ingredient in the study drug Vesanoid cannot take part.
People with malabsorption syndrome cannot take part. This means the body has trouble absorbing nutrients or medicine from the gut.
People who cannot swallow oral medicine cannot take part.
Pregnant women cannot take part.
Women who are breastfeeding cannot take part.
People who must take vitamin A, tetracyclines (a type of antibiotic), other retinoids, anti-fibrinolytic agents (medicine that helps prevent bleeding from broken blood clots), or strong medicines that speed up or slow down CYP3A4 (a liver enzyme that breaks down many medicines) cannot take part.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut De Cancerologie De Lorraine	Vandoeuvre Les Nancy	France
Institut Gustave Roussy	Villejuif	France
Azienda Ospedaliero Universitaria Careggi	Florence	Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy

Other Sites

Site Name	City	Country
Centre Antoine Lacassagne	Nice	France
Hopital Tenon	Paris	France
Azienda Ulss 3 Serenissima	Venice	Italy
Institut Godinot	Reims	France
Hopital Beaujon	Clichy	France
Hopital Nord Franche-Comte	Belfort	France
Institut de Cancérologie de l’Ouest	Saint-Herblain	France
Chbogicat Uiognbucvwyaic Sjveustjz	Woluwe-Saint-Lambert	Belgium
Hkupeioss Mcornflj Sitpmo	Milan	Italy
Bmcfhbka Umwnshdsbz Hocfmovr Cdeifl	Besançon	France
Cxkbge Lqsa Bxnzpo	Lyon	France
Coquab Oqzqi Lpskcdy	Lille	France

Trial status

Country	Status	Recruitment Start
Belgium	Not yet recruiting	04.07.2024
France	Recruiting	04.07.2024
Italy	Not yet recruiting	04.07.2024

Trial locations

Investigated drugs:

Cisplatin is a chemotherapy medicine given through a vein. In this trial, it is used as part of the standard treatment to help destroy cancer cells and make the radiotherapy work better.

Cetuximab is a targeted cancer treatment given through a vein. It is used to block signals that help cancer cells grow and survive, and it is part of the background treatment in this study.

Tretinoin is an oral medicine used in this trial as the study treatment. It is a form of vitamin A and is being tested to see whether it can improve treatment results when added to radiotherapy and other cancer therapy.

Investigated diseases:

Laryngeal squamous cell carcinoma – A cancer that starts in the flat cells lining the larynx, also called the voice box. It usually begins as a localized growth and may slowly spread into nearby tissues, nearby lymph nodes, and then other parts of the body. Common sites of spread include the throat, neck nodes, and distant organs.

Hypopharyngeal squamous cell carcinoma – A cancer that develops in the flat cells of the hypopharynx, the lower part of the throat behind the larynx. It often begins in one area and can extend to nearby structures as it grows. Over time, it may spread to nearby lymph nodes and, in some cases, to distant parts of the body.

Oropharyngeal squamous cell carcinoma – A cancer arising from the flat cells of the oropharynx, the middle part of the throat behind the mouth. It typically starts as a local lesion and may gradually invade nearby tissues. As it progresses, it can spread to nearby neck lymph nodes and sometimes beyond the head and neck region.

Trial ID:

2022-501315-13-00

Protocol code:

LYSARI/ET22-156

Trial Phase:

Therapeutic confirmatory (Phase III)

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Evaluation of Lymphocyte-Sparing Radiotherapy and All-Trans Retinoic Acid in Lateralized Oropharyngeal, Laryngeal, and Hypopharyngeal Squamous Cell Carcinoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?