NON-RESECTABLE LOCALLY ADVANCED HPV NEGATIVE HNSCC MedDRA version: 21.1 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DURVALUMAB
CAS Number: 1428935-60
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
Charite Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with locally advanced histopathologically confirmed HNSCC not candidate for primary surgical treatment ? No distant metastasis (M0) ? Patients that are planned for radiotherapy ? Tumor tissue available for central testing Patients with HPV/p16 negative disease (=70% positively stained cells) as determined by central testing ? Adequate normal organ and marrow function ? Measurable tumor according to RECIST ? Patients must be expected to complete the treatment. ? Age > 18 years at time of study entry ? Female patients must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry and be willing to use adequate contraceptive measurements as described in the protocol ? Non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to use adequate contraceptive measurements as described in the protocol 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 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: ? ? •Participation in another clinical study with an investigational product during the last 3 months •Prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumor reductive surgery, neo-adjuvant chemotherapy, EGFR inhibitors or radiotherapy). •Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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: oPatients with vitiligo or alopecia oPatients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement oAny chronic skin condition that does not require systemic therapy oPatients without active disease in the last 5 years may be included but only after consultation with the study physician oPatients with celiac disease controlled by diet alone •History of primary immunodeficiency •History of allogeneic organ transplant •History of another primary malignancy except for oMalignancy 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 oAdequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease oAdequately treated carcinoma in situ without evidence of disease •History of hypersensitivity to durvalumab or any excipient •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 •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. •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control as described in the protocol from screening to 90 days after the last dose of durvalumab monotherapy •Distant metastasis •Patients who are institutionalised by official order •Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s Correction •Receipt of live attenuated vaccination within
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to explore the feasibility and efficacy in terms of treatment discontinuation due to toxicity and in terms of 1-year progression free survival of a PDL1-Inhibitor plus a CTLA-4 Inhibitor in combination with radiotherapy vs a PDL1-Inhibitor in combination with radiotherapy as first-line therapy for patients with non-resectable locally advanced HNSCC in the poor prognostic subgroup. ;Secondary Objective: Secondary objectives are to investigate the benefit of the addition of a CTLA-4 Inhibitor and/or a PDL1-Inhibitor to radiotherapy in terms of overall progression free survival, overall survival and to investigate the approach in terms of safety, chronic toxicity and quality of life;Primary end point(s): The primary endpoints are the 1-year progression free survival composed of the 1-year in-field-progression-free survival and 1-year distant metastasis free survival and the number of treatment discontinuations due to toxicity;Timepoint(s) of evaluation of this end point: The primary endpoint of the trial will be analysed when data is mature (1 year after last patient has stopped treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Overall Survival ? Safety ? Chronic toxicity ? Quality of life;Timepoint(s) of evaluation of this end point: Secondary endpoint will be analysed when data are mature (at least 1 year after last patient has stopped treatment) | — |
Countries
Germany
Contacts
Public ContactCharité Comprehensive Cancer Center
Charité Universitätsmedizin Berlin
Outcome results
None listed