Oropharynx CancerPhase 3LYSARINCT06706401
Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma
A Phase 3 study testing Vesanoid, Standard radiotherapy and Tailored radiotherapy in people with Oropharynx Cancer and Larynx Cancer, run by Centre Leon Berard at 8 sites in France.
Trial summary
The aim of this study is to investigate the effect of ATRA (Vesanoid) and the effect of tailored radiotherapy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oropharynx Cancer, Larynx Cancer, Hypopharynx Cancer
- What is being tested?
- Vesanoid, Standard radiotherapy and Tailored radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 460 participants
- Where
- 8 sitesFrance
- Study dates
- 20 Feb 2025to Jan 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- I1. Male or female patients aged ≥ 18 years old at time of inform consent signature.
- I2. Patients with primary head and neck tumour up to, but not crossing the midline, previously untreated with histologically-confirmed squamous cell carcinoma of:
- the oropharynx p16-, larynx or hypopharynx : T1/N2a-N2b, T2/N0-N2b, T3/N0-N2b (UICC 8th Ed.), or
- the oropharynx p16+ : T1/N1 (multiple nodes), T2-T3/N0-N1 (UICC 8th Ed.).
- I3. Patients with lymph node staging assessed by an FDG-PET/CT with no contralateral nodal uptake.
- I4. Patients amenable to treatment with RT or concomitant chemo-radiotherapy as decided by the treating physician as a function of tumor stage, tumor location, performance of the patients.
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- I5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
- I6. Adequate hematologic and end-organ function, defined by the following laboratory test results obtained within 7 days prior to randomisation :
- Hematological (without transfusion within 2 weeks) :
- Neutrophils count > 1.5 × 109 /L
- Platelets count > 75 × 109 /L
- WBC≥ 3.0 × 109 /L
- Hepatic function :
- Total Bilirubin < 1.5 × ULN (except for Gilbert's syndrome which will allow bilirubin ≤ 3 ULN).
- Alanine aminotransferase (ALT) ≤ 2.5 × ULN.
- Aspartate aminotransferase (AST) ≤ 2.5 × ULN.
- Albumin >3.0g/dL
- Renal function :
- Serum creatinine < 1.5 ×ULN.
- I7. QTcF ≤450ms for men and 470ms for women, from 3 electrocardiograms on screening ECG, within 7 days prior randomisation.
- I8. Women patients of child-bearing potential are eligible, provided they have a negative serum or urine pregnancy test within 7 days prior randomisation, and agrees to use adequate contraception for up to 1 month after the end of study treatments.
- I9. Fertile men must agree to use an effective method of contraception during the study and for up to 1 month after the end of study treatments.
- I10. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed and should be able and willing to comply with study visits and procedures as per protocol.
- I11. Patients must be covered by a medical insurance in country where applicable.
Who cannot join
- E1. Patient with primary tumor crossing the midline or patients with bilateral primary tumors.
- E2. Patients with T1-N0 (p16-), T1-N1 (p16-), T1-N0 (p16+), T4 (p16- and p16+), bilateral lymph nodes or nodal disease more than 6 cm (p16- and p16+).
- E3. Patients with unknown primary tumor size as per TNM i.e. T0-N1 to T0-N3, p16- or p16+.
- E4. Patients with contralateral FDG-PET/CT nodal uptake.
- E5. Patient with any previous anti-cancer therapy for HNSCC (all prior treatment are forbidden: chemotherapy, radiotherapy, targeted therapy, immunotherapy or any other therapy approved or experimental).
- E6. Patient with malignancies other than HNSCC within 3 years prior to randomisation with the exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer treated surgically with curative intent.
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- E7. Patient with ongoing or anticipation of need for systemic immunosuppressive medication (including, but not limited to, glucocorticoids, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents); with the exceptions of intranasal, inhaled or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
- E8. Patient with ongoing or anticipation of need for systemic immunostimulatory agents (including, but not limited to, interferons and IL-2).
- E9. Patient with concurrent treatment with any other anti-cancer treatment, approved or investigational agent or participation in another clinical trial with therapeutic intent.
- E10. Patient with infectious diseases :
- Severe infection within 4 weeks prior to randomisation, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia,
- Active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening),
- Active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at screening,
- HIV infection,
- Active tuberculosis.
- E11.Patient with any psychological, cognitive, familial, sociological or geographical condition potentially hampering compliance with the study protocol, completion of patient reported measures and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
- E12. Patient with known hypersensitivity to tretinoin, other retinoids, soya, peanut or to any of the excipients of vesanoid.
- E13. Patient with known malabsorption syndrome and/or unable to swallow oral medication.
- E14.Patient with ongoing or expected need for concomitant treatment with vitamin A, tetracyclines, other retinoids, anti-fibrinolytic agent, and strong inducers or inhibitors of CYP3A4.
- E15.Pregnant or lactating woman.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
France8 sites, 8 recruiting
- Recruiting
Institut de Cancérologie de l'Ouest - Paul Papin
Angers, 49055
Aurore Goineau, PhD, +33241352830, aurore.goineau@ico.unicancer.fr
Aurore Goineau, PhD
- Recruiting
Centre Oscar Lambret
Lille, 59000
Xavier Liem, PhD, +33320295911, x-liem@o-lambret.fr
Xavier Liem, PhD
- Recruiting
Centre Léon Bérard
Lyon, France, 69008
Vincent Grégoire, PhD, 4 69 85 62 53 ext. +33, vincent.gregoire@lyon.unicancer.fr
Vincent Grégoire, PhD
- Recruiting
Centre Antoine Lacassagne
Nice, 06189
Deborah Aloi, PhD, +33492031000, deborah.aloi@nice.unicancer.fr
Deborah Aloi, PhD
- Recruiting
AP-HP - Hôpital Tenon
Paris, 75020
Florence Huguet, PhD, +33156016210, florence.huguet@aphp.fr
Florence Huguet, PhD
- Recruiting
Institut Godinot
Reims
Arnaud BEDDOCK, PhD, +33326504351, arnaud.beddok@reims.unicancer.fr
Arnaud BEDDOCK, PhD
- Recruiting
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, France, 54519
Maria JOLNEROVSKI, PhD, 83598423 ext. +33, m.jolnerovski@nancy.unicancer.fr
Maria JOLNEROVSKI, PhD
- Recruiting
Institut Gustave Roussy
Villejuif, France, 94805
Roger Sun, PhD, 1 42 11 25 16 ext. +33, ROGER.SUN@gustaveroussy.fr
Roger Sun, PhD
About this study
Official title: A Multicenter, Randomised 2*2 Factorial Design Comparing Standard to Reduced-target Volume Radiotherapy With or Without All-trans Retinoic Acid (ATRA) in Patients With Lateralised Oropharyngeal, Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.
The aim of this study is to investigate the effect of ATRA (Vesanoid) and the effect of tailored radiotherapy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx.
Read the detailed description
Following validation of eligibility criteria, patients will be randomised (1:1:1:1) to receive:
- Arm A: Standard radiotherapy then follow-up
- Arm B: Tailored radiotherapy and ATRA (Vesanoid)
- Arm C: Standard radiotherapy and ATRA (Vesanoid)
- Arm D: Tailored radiotherapy then follow-up
This randomised phase III clinical trial will provide the clinical proof-of-concept that unilateral irradiation for lateralized tumors and the addition of ATRA (Vesanoid) to radiotherapy in HNSCC prevents severe lymphopenia and immunosenescence and therefore, may foster a radiation-induced anticancer immune response sufficient to increase event-free survival at 2 years.
- Keywords
- Localised squamous cell carcinoma of head and neck, Previously untreated, Standard radiotherapy, Tailored radiotherapy, Vesanoid
- Medical subject headings
- Oropharyngeal Neoplasms, Laryngeal Neoplasms, Hypopharyngeal Neoplasms, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VesanoidDrug
Also called ATRA
Before (chemo)radiotherapy: D1 to D3: 150mg/m2/day, 1 week before radiotherapy. Post (chemo)radiotherapy: D1 to D3: 150mg/m2/day every 3 weeks for up to 4 cycles post (chemo)radiotherapy
Standard radiotherapyRadiation
70 Gy in 35 fractions of 2 Gy over 6 (6 fractions per week) or hyperfractionated RT with a median therapeutic dose of 80.5 Gy delivered in 70 fractions of 1.15 Gy over 7 weeks.
Tailored radiotherapyRadiation
70 Gy in 35 fractions of 2 Gy over 6 weeks (6 fractions per week) or hyperfractionated RT with a median therapeutic dose of 80.5 Gy delivered in 70 fractions of 1.15 Gy over 7 weeks.
CisplatinDrug
Cisplatin is recommended for the following patients : Stage T1-T2/N2a-N2b and T3/N0-N1-N2a-N2b. concomitant chemotherapy is standard of care treatments and should be administered as per standard practice.
Chemotherapy will include one of the two cisplatin regimens specified in this protocol at the discretion of the participating centers. The centers must however treat all their recruited patients with one of the two regimens chosen before site activation. Chemotherapy should start the first day of radiotherapy. Cisplatin should be infused before radiation therapy delivery.
The 2 options are:
- Cisplatin 100 mg/m² i.v. on day 1 and 22 of radiotherapy (when 70 Gy are delivered in 6 weeks) or on day 1, 22 and 43 (when 70 Gy are delivered in 7 weeks). or
- Cisplatin 40 mg/m² i.v. on day 1, 8, 15, 22, 29, 35 of radiotherapy (when 70 Gy are delivered in 6 weeks) or on day 1, 8, 15, 22, 29, 35, 42 of radiotherapy (when 70 Gy are delivered in 7 weeks).
CetuximabDrug
Cetuximab is recommended for the following patients : Stage T1-T2/N2a-N2b and T3/N0-N1-N2a-N2b. concomitant Cetuximab is standard of care treatments and should be administered as per standard practice.
Cetuximab therapy will be started with an intravenous loading dose of 400 mg/m2 one week before start of RT followed by six (radiotherapy over 6 weeks) or seven (radiotherapy over 7 weeks) weekly doses of 250 mg/m2.
| Study group | Role | What they receive |
|---|---|---|
| Standard radiotherapy | Active comparator | Patient will receive 6 to 8 weeks of standard (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first).
In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Receives: Radiation: Standard radiotherapy; Drug: Cisplatin; Drug: Cetuximab |
| Tailored radiotherapy and ATRA (Vesanoid) | Experimental | ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). Then, patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy. In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Receives: Drug: Vesanoid; Radiation: Tailored radiotherapy; Drug: Cisplatin; Drug: Cetuximab |
| Standard radiotherapy and ATRA (Vesanoid) | Experimental | ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments).Then, patient will receive 6 to 8 weeks of standard (chemo)radiotherapy. Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Receives: Drug: Vesanoid; Radiation: Standard radiotherapy; Drug: Cisplatin; Drug: Cetuximab |
| Tailored radiotherapy | Experimental | Patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first).
In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Receives: Radiation: Tailored radiotherapy; Drug: Cisplatin; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival (EFS)
Event free survival (EFS) is defined as the time from randomisation to apparition of a documented relapse either local or regional or distant according to clinical or radiological assessment, or persistent residual disease including pathologically positive neck node, or death due to any cause.
Measured: At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years
Secondary outcomes (12)
Local relapse Free Survival
Local relapse Free Survival (lrFS, at site of primary tumor) is defined as the delay from randomisation to first local relapse (i.e. primary site) or death. Patients without documented event will be censured at the last adequate visit or tumor evaluation.
Measured: At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years
Regional relapse Free survival
Regional relapse Free survival (rrFS, in the neck) is defined as the delay from randomisation to first regional relapse (i.e. neck) or death.
Measured: At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years
Metastasis Free Survival
Metastasis Free Survival (mFS) is the time between randomisation and apparition of first metastasis (date of metastatic diagnosis). Patients without documented event will be censured at the last tumour evaluation.
Measured: At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years
Rate of pathologically positive lymph nodes
Rate of pathologically positive lymph nodes at neck node dissection performed at 4 months after the completion of (chemo)-radiotherapy for those patients benefiting from a neck node dissection
Measured: At 4 months from the completion of (chemo)-radiotherapy
Event Free Survival (EFS)
Event Free Survival (EFS) considering that pathologically positive neck node within 4 months post-randomisation will not be an event.
Measured: At 4 months from the completion of (chemo)-radiotherapy
Overall survival
Overall survival defined as the time from randomisation to death due to any cause. Patient without documented death at the time of analysis will be censored at the date of last known contact.
Measured: Until up to 2 years follow-up of the last patient enrolled
Adverse events
Incidence of any adverse events graded according to NCI-CTCAE V5.0
Measured: From the date of first intake of study drug until 27 months after the randomisation of the last randomised patient
Patient quality of life (EORTC QLQ-C30)
To assess the impact of the proposed combinations on patient' quality of life in the target population (EORTC QLQ-C30)
Measured: At randomisation, at 6, 9, 15, 21 and 27 months after randomisation and30 days after the last study treatments administration
Patient quality of life (EQ5-DL)
To assess the impact of the proposed combinations on patient' quality of life in the target population (EQ5-DL)
Measured: At randomisation, at 6, 9, 15, 21 and 27 months after randomisation and30 days after the last study treatments administration
Patient quality of life (EORTC QLQ-H&N43)
To assess the impact of the proposed combinations on patient' quality of life in the target population (EORTC QLQ-H\&N43)
Measured: At randomisation, at 6, 9, 15, 21 and 27 months after randomisation and30 days after the last study treatments administration
Health economic analysis
To perform an economic analysis of the use of a tailored-RT with or without ATRA (Vesanoid). A cost-effectiveness methodology will be implemented, which involves computing costs and efficacy for each of the four treatment arms.
Measured: From the first patient enrolled to 2 years after treatment discontinuation of the last patient enrolled
Immunomonitoring
To study the impact of treatment on lymphocytes number and function, including by assessing immunosenescence induction and to study blood biomarkers predictive of response/toxicity following treatment
Measured: Cycle 1 Day 1 pre-dose of Vesanoid, Day 1 of radiotherapy and end of radiotherapy (8 to 10 weeks after randomisation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2024
- Study start20 Feb 2025
- Primary completionJan 2029 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Oropharynx CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- This trial is a 2\*2 factorial design, multicentric, randomised, Phase III study
- Masking
- None (open label)
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent Grégoire, PhD, Principal investigator, Centre Leon Berard
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06706401
- Sponsor's protocol ID
- ET 22-156
- Acronym
- LYSARI
- Status last verified
- Apr 2026
- First submitted
- 19 Nov 2024
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gau M, Alfaraj FA, Huang SH, O'Sullivan B, Su J, Xu W, Hamilton SN, Maletta A, Salman O, McInerney M, Javed A, Sanz-Garcia E, Bratman S, Hahn E, Hope A, Kim JJ, Malik N, McPartlin A, Tsai CJ, Waldron J, Yao CMKL, de Almeida JR, Hosni A. Unilateral vs bilateral neck irradiation: The importance of careful patient selection in tailoring radiation therapy for lateralized palatine-tonsil and non-palatine-tonsil oropharyngeal carcinoma. Radiother Oncol. 2025 Sep;210:111049. doi: 10.1016/j.radonc.2025.111049. Epub 2025 Jul 19.
PubMed 40692081