Etude : REWRITe /

ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.

Type d'étude
Présentation de l'étude
Acronyme : REWRITe

Nom :

Traitement : Métastatique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 26/03/2020
CIM10 - Localisation(s)
Informations principales
Titre : Essai de phase II évaluant l’association radiothérapie-durvalumab sans irradiation prophylactique cervicale dans les carcinomes épidermoïdes de la tête et du cou

Spécialité : Lèvre, cavité buccale et pharynx
Localisation : C10 - Tumeur maligne de l'oropharynx

Spécialité : Lèvre, cavité buccale et pharynx
Localisation : C13 - Tumeur maligne de l'hypopharynx

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C32 - Tumeur maligne du larynx

Spécialité : Lèvre, cavité buccale et pharynx
Localisation : C14 - Tumeur maligne de la lèvre, de la cavité buccale et du pharynx, de sièges autres et mal définis
Informations complémentaires
Schéma : Experimental: RT-durvalumab
durvalumab at fixed dose of 1120 mg on Day1 of RT and every 3 weeks during the RT. Durvalumab with be continued at a fixed dose of 1500 mg every 4 weeks during 6 months following RT.
Intervention: Drug: Durvalumab

Phase : II

Stade : Localisé à Localement avancé

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : Age > 18 years with no upper limit
Performance Status ECOG 0-2
Non-eligible to existing SOC with chemo-RT or cetuximab-RT
Squamous cell carcinoma, previously untreated
T1-T2 N0 with measurable disease for whom the risk of nodal spread is estimated to be low (< 10-15%) or T3-T4 N0 with measurable disease for whom large field neck irradiation may not be appropriate due to age, and/or fragile condition (PS2)
N0 neck based on clinical, MRI and FDG/PET-CT examinations
Oral cavity, oropharynx, hypopharynx or larynx
Availability of pre-treatment tumor tissue sample (for PD-L1 expression, TILs and immune landscape)
Documentation of p16 disease (HPV status for oropharyngeal tumor)
Recording of alcohol consumption and smoking history
Adequate normal organ and marrow function as defined below:
1. Hemoglobin > 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1500 per mm3 3. Platelet count > 100 000 per mm3 4. Serum bilirubin < 1.5 x institutional upper limit of normal (ULN) 5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN 12.Measured creatinine clearance (CL) >40 mL/min (CKD-EPI method recommended) or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula 13. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations during the follow up period 14. Patient able to understand French and complete the quality of life questionnaires 15.Must have a life expectancy of at least 12 weeks 16. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following agespecific requirements apply:

Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
17. Patient capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.

Critères de non-inclusion : Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
Metastatic disease
Active CNS disease
Any prior or current treatment for invasive head and neck cancer
Any unresolved toxicity NCI CTCAE v5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator
Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
History of leptomeningeal carcinomatosis
Body weight ≤ 30 kg and/or weight loss of ≥ 15% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
Concomitant treatment with any drug on the prohibited medication list such as live vaccines within 30 days prior to the first dose of IP
Known allergy or hypersensitivity reaction to study drug or any of the study drug excipients
Prior organ transplantation including allogenic stem-cell transplantation
Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis
Active autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc])
Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
History of another primary malignancy except for:

Malignancy treated with curative intent and with no known active disease ≥ 5 years
Adequately treated non-melanoma skin cancer
Adequately treated carcinoma in situ without evidence of disease
History of active primary immunodeficiency
Ongoing or active infection including tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

Intranasal, inhaled, topical steroids, or local steroid injections
Systemic corticosteroids < 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment
Informations relatives au promoteur
Promoteur :
Groupe Oncologie Radiothérapie Tête et Cou (GORTEC)
Type de sponsor : Institutionnel
37000 TOURS

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre de radiothérapie G. Le Conquérant - 61 rue Denfert Rochereau - 76600 LE HAVRE

Investigateur :
Dr Laurent MARTIN

Non communiqué

Statut de l'essai : OUVERT

MAJ : 26/03/2020