Treatment for head and neck cancer using tailored radiotherapy and ATRA

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.

This study is testing if a new combination of a cancer drug called ATRA with personalized radiotherapy can help people with certain types of head and neck cancer live longer and feel better.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 460 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Leon Berard (other)
• Drugs / interventions: chemotherapy, immunotherapy, methotrexate, cyclophosphamide, prednisone, radiation
• Locations: 8 sites (Lyon, France and 7 other locations)
• Trial ID: NCT06706401 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial aims to evaluate the effectiveness of ATRA (Vesanoid) combined with tailored radiotherapy in patients with localized squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Participants will be randomly assigned to one of four treatment arms: standard radiotherapy, tailored radiotherapy, or combinations with ATRA. The study seeks to determine if these approaches can reduce severe lymphopenia and enhance the immune response, potentially improving event-free survival rates at two years. The trial will include patients with specific tumor characteristics and performance status.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with untreated, localized squamous cell carcinoma of the head and neck that meets specific staging criteria.

Not a fit: Patients with tumors crossing the midline or those with advanced disease not amenable to the specified treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and reduce side effects for patients with head and neck cancer.

How similar studies have performed: Other studies have shown promise in using tailored radiotherapy and immunotherapy approaches, but this specific combination is novel.

Eligibility criteria

Inclusion criteria :

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.

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.

Exclusion criteria :

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.

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.

Where this trial is running

Lyon, France and 7 other locations

• Centre Léon Bérard — Lyon, France, France (RECRUITING)
• Institut de Cancérologie de Lorraine — Vandœuvre-lès-Nancy, France, France (RECRUITING)
• Institut Gustave Roussy — Villejuif, France, France (RECRUITING)
• Institut de Cancérologie de l'Ouest - Paul Papin — Angers, France (RECRUITING)
• Centre Oscar Lambret — Lille, France (RECRUITING)
• Centre Antoine Lacassagne — Nice, France (RECRUITING)
• AP-HP - Hôpital Tenon — Paris, France (RECRUITING)
• Institut Godinot — Reims, France (RECRUITING)

Study contacts

• Principal investigator: Vincent Grégoire, PhD — Centre Leon Berard
• Study coordinator: Vincent Grégoire, PhD

Conditions: Oropharynx Cancer, Larynx Cancer, Hypopharynx Cancer, Primary Head and Neck Tumor, Localised squamous cell carcinoma of head and neck, Previously untreated, Standard radiotherapy, Tailored radiotherapy