Informations générales (source: ClinicalTrials.gov)
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.
Interventional
Phase 3
Centre Leon Berard (Voir sur ClinicalTrials)
février 2025
janvier 2029
12 septembre 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Roger Sun, PhD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Léon Bérard - 69008 - Lyon - France | Vincent Grégoire, PhD | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
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.