None listed
Conditions
Interventions
Drug : Durvalumab monotherapy Arm
Patients in the durvalumab (MEDI4736) monotherapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) once prior to surgery in this study. After surgical
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed stage II-IV operable HNSCC oral cavity, hypopharynx, oropharynx, larynx • Measurable disease defined as lesions that can be accurately measured by RECIST 1.1. • Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations • Age >18 years at time of study entry or Adult male or female • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 • Body weight >30kg • Life expectancy of at least 12 weeks • Adequate normal organ and marrow function as defined below: o Haemoglobin =9.0 g/dL o Absolute neutrophil count (ANC) > 1500 per mm3 o Platelet count >75,000 per mm3 o Serum bilirubin =1.5 x institutional upper limit of normal (ULN). o AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN o Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85 72 x serum creatinine (mg/dL) ? 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). • Patient 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.
Exclusion criteria
Exclusion criteria: ? Involvement in the planning and/or conduct of the study ? Participation in another clinical study with an investigational product during the last ? ? 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 ? Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non–cancer-related conditions (e.g., hormone replacement therapy) is acceptable. ? Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria o Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. o Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician. ? 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]). The following are exceptions to this criterion: ? Patients with vitiligo or alopecia ? Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement ? Any chronic skin condition that does not require systemic therapy ? Patients without active disease in the last 5 years may be included but only after consultation with the study physician ? Patients with celiac disease controlled by diet alone ? 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 o 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 o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease o 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| locoregional relapse rate;Distant metastaic rate | — |
Secondary
| Measure | Time frame |
|---|---|
| safety;distant metastases free survival;locoregional control time;progression-free survival, PFS | — |
Countries
Korea, Republic of
Contacts
Public ContactYuri Kang
Yonsei University Health System, Severance Hospital
Outcome results
None listed