Locally advanced head and neck squamous cell carcinoma (HNSCC) MedDRA version: 21.1 Level: LLT Classification code 10026518 Term: Malignant neoplasm of supraglottis stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10026519 Term: Malignant neoplasm of supraglottis stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA versio
Conditions
Interventions
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DURVALUMAB
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Conce
Sponsors
Dean of the Medical Faculty of the Friedrich-Alexander University Erlangen-Nürnberg Prof. Dr. Markus Neurath
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening Evaluations Age > 18 years at time of study entry Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (amend based on specific study) Locally advanced HNSCC, UICC stage III-IVB (oral cavity, oropharynx, hypopharynx, supraglottic larynx) (according to TNM version 8) Histological confirmation of HNSCC (regardless if p16 positive or negative) Measureable CD8 density in provided archival tumor tissue Body weight >30kg Adequate normal organ and marrow function as defined: Haemoglobin = 9.0 g/dL; White blood cells (WBC) = 3,000 per mm3; Platelet count >100,000 per mm3 Serum bilirubin = 1.5 x institutional upper limit of normal (ULN) AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal (ULN) Creatinine Clearance >40ml/min (calculated from serum creatinine or cystatin C, alternatively 24h urine possible) 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) Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) Participation in another clinical study with an investigational product during the last 4 weeks Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study Distant metastases Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) of the locally advanced HNSCC Any other concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment, except the induction chemotherapy in the protocol. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable Prior radiotherapy of HNSCC Radiotherapy to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug Major surgical procedure of the current locally advanced HNSCC (as defined by the Investigator). Note: Local surgery of isolated lesions for palliative intent is acceptable History of allogenic organ Transplantation Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).(eceptions , see protocol) Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, 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 before the first dose of IP and of low potential risk for recurrence - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease History of active primary immunodeficiency Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), 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 or tremelimumab. (exceptions, see protocol) Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of the feasibility of a new treatment scheme with induction Chemo-Immuno-Therapy followed by Radio-Immuno-Therapy Assessment of the predictive character of changes of CD8+ tumor infiltrating immune cells after induction chemo-immunotherapy;Secondary Objective: Assessment of the efficacy of a Radio-Immuno-Therapy with durvalumab and tremelimumab Assessment of predictive value and changes of different tumor infiltrating immune cells and immunological tumor markers. Longitudinal analysis of the immune phenotype in the peripheral blood.;Primary end point(s): Assessment of the number of participants receiving the protocol treatment until cycle 6 of antibody treatment Feasibility means the number of participants receiving the protocol Treatment Assessment of the predictive character of changes of CD8+ tumor infiltrating immune cells after induction chemoimmunotherapy Assessment of the absence of any dose-limiting toxicities;Timepoint(s) of evaluation of this end point: End of follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression free survival Pathologically confirmed Response Overall survival Assessment of predictive value of different tumor infiltrating immune cells and immunological tumor markers Assessment of predictive changes of different tumor infiltrating immune cells and immunological tumor markers ;Timepoint(s) of evaluation of this end point: 12 weeks after completion of radiotherapy] Baseline (week 0), each cycle is 4 weeks, at the end of cycle 1 (week 2), cycle 2 (week 6), cycle 3 (week 10), cycle 4 (week 14), cycle 5-12 (up to 2 years)] | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat
University Hospital Erlangen
Outcome results
None listed