Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma

NCT06706401 | Recruiting Phase 3 DMC

• 1 other identifier: ET 22-156
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Primary Head and Neck Tumor; Oropharynx Cancer; Larynx Cancer; Hypopharynx Cancer

Keywords

Localised squamous cell carcinoma of head and neck; Previously untreated; Standard radiotherapy; Tailored radiotherapy; Vesanoid

Outcome Measures

Primary Outcomes (1)

• 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.

  At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years

Secondary Outcomes (12)

• Local relapse Free Survival

  At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years

• Regional relapse Free survival

  At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years

• Metastasis Free Survival

  At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years

• Rate of pathologically positive lymph nodes

  At 4 months from the completion of (chemo)-radiotherapy

• Event Free Survival (EFS)

  At 4 months from the completion of (chemo)-radiotherapy

Study Arms (4)

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).

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).

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).

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).

Radiation: Tailored radiotherapy; Drug: Cisplatin; Drug: Cetuximab

Interventions

Vesanoid DRUG

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

Also known as: ATRA

Standard radiotherapy and ATRA (Vesanoid); Tailored radiotherapy and ATRA (Vesanoid)

Standard radiotherapy RADIATION

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.

Standard radiotherapy; Standard radiotherapy and ATRA (Vesanoid)

Tailored radiotherapy RADIATION

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.

Tailored radiotherapy; Tailored radiotherapy and ATRA (Vesanoid)

Cisplatin DRUG

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).

Standard radiotherapy; Standard radiotherapy and ATRA (Vesanoid); Tailored radiotherapy; Tailored radiotherapy and ATRA (Vesanoid)

Cetuximab DRUG

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.

Standard radiotherapy; Standard radiotherapy and ATRA (Vesanoid); Tailored radiotherapy; Tailored radiotherapy and ATRA (Vesanoid)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (8)

Centre Léon Bérard

Lyon, France, 69008, France

RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France, 54519, France

RECRUITING

Institut Gustave Roussy

Villejuif, France, 94805, France

RECRUITING

Institut de Cancérologie de l'Ouest - Paul Papin

Angers, 49055, France

RECRUITING

Centre Oscar Lambret

Lille, 59000, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

AP-HP - Hôpital Tenon

Paris, 75020, France

RECRUITING

Institut Godinot

Reims, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 40692081 DERIVED

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Laryngeal Neoplasms; Hypopharyngeal Neoplasms; Head and Neck Neoplasms

Interventions

Tretinoin; Cisplatin; Cetuximab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vincent Grégoire, PhD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent Grégoire, PhD

CONTACT

4 69 85 62 53; vincent.gregoire@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial is a 2\*2 factorial design, multicentric, randomised, Phase III study

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: November 26, 2024
• Study Start: February 20, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

FR (8)