Untreated Squamous cell carcinoma : Oral cavity, oropharynx, hypopharynx or larynx MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
GORTEC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age > 18 years with no upper limit 2. Performance Status ECOG 0-2 3. Non-eligible to existing SOC with chemo-RT or cetuximab-RT 4. Squamous cell carcinoma, previously untreated 5. T1-T2 N0 with measurable disease for whom the risk of nodal spread is estimated to be low ( 9.0 g/dL - Absolute neutrophil count (ANC) = 1500 per mm3 - Platelet count > 100 000 per mm3 - Serum bilirubin 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 age-specific requirements apply: - Women 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers 2. Metastatic disease 3. Active CNS disease 4. Any prior or current treatment for invasive head and neck cancer 5. 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. a. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator 6. 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 7. History of leptomeningeal carcinomatosis 8. Body weight = 30 kg and/or weight loss of = 15% during the last 4 weeks (except if re-nutrition with a feeding tube is planned before the onset of treatment or is ongoing) 9. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol 10. Concomitant treatment with any drug on the prohibited medication list such as live vaccines within 30 days prior to the first dose of IP 11. Known allergy or hypersensitivity reaction to study drug or any of the study drug excipients 12. Prior organ transplantation including allogenic stem-cell transplantation 13. Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis 14. 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]) 15. 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 16. History of another primary malignancy except for: a. Malignancy treated with curative intent and with no known active disease = 5 years b. Adequately treated non-melanoma skin cancer c. Adequately treated carcinoma in situ without evidence of disease 17. History of active primary immunodeficiency 18. 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 19. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections b. Systemic corticosteroids < 10 mg/day of prednisone or its equivalent c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate: •Tolerance and safety of durvalumab combined with RT, as early and late treatment-related adverse events of grade = 2 according to the NCI CTCAE V5.0 •Local control (i.e. primary tumor site) •Locoregional (neck) control •Ultimate neck control including salvage surgery and/or RT in case of nodal relapse •Distant metastases control •Overall survival •Objective Response Rate •Progression-free survival •Health-related quality of life •Immune or biological markers potentially associated with patient outcome ;Primary end point(s): Regional (neck) nodal control rate ;Timepoint(s) of evaluation of this end point: 1 year after treatment;Main Objective: To evaluate the regional (neck) nodal control of durvalumab in combination with RT restricted to the primary tumor and the immediately adjacent nodal level (i.e. without prophylactic neck irradiation) in N0 patients with SCCHN. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Early and late adverse events of grade = 2, according to the CTCAE V5.0 • Local control at the primary site • Locoregional nodal + primary site control rate • Distant metastases control rate • Ultimate regional control including salvage surgery and/or salvage RT) • Overall survival • Objective Response Rate • Progression-free survival • QLQ C30 and QLQ-H&N35 scores at baseline, 3, 15 and 27 months post RT;Timepoint(s) of evaluation of this end point: During treatment | — |
Countries
France, Switzerland
Contacts
Public ContactCécile MICHEL
GORTEC
Outcome results
None listed