local squamous cell carcinoma of the head and neck MedDRA version: 21.0 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) 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
Trade Name: Tecentriq
Product Name: Atezolizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Other descriptive name: MP
Sponsors
University Hospital Essen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria 1. 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 has to be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. If laboratory or imaging procedures were performed for alternate reasons prior to signing consent, these can be used for screening purposes with consent of the patient. However, all screening examinations and laboratory results must have been obtained within 14 days before first study drug administration (initial tumor imaging: within 28 days before first study drug administration). 2. Only patients for whom sufficient tumor material to be judged by the local investigator and which is of adequate quality can be included into the trial. Please refer to section 6.5 for further details on quantity and quality of tumor samples. 3. Histologically or cytologically proven SCCHN (cT1-4a, cN0-3, cM0) that is amenable to surgical resection with curative intent based on the decision of the local multidisciplinary tumorboard. 4. Patients with relapse after primary radio(chemo)-therapy are allowed if a salvage surgery is possible (maximum 20%). Patients should have recovered from the effects of radiation: AE/sequelae should resolves to = grade 2 (no minimum recovery period required). 5. Male or female, 18 years of age or older on day of signing informed consent 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 7. Life expectancy >12 weeks 8. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: • Absolute neutrophil count (ANC) = 1.5E9/L without granulocyte colony-stimulating factor support • Lymphocyte count = 0.5E9/L • Platelet Count = 100E9/L without transfusion • Hemoglobin = 90 g/L o Patients may be transfused to meet this criterion but patients in need of chronic or repeated RBC transfusion should be discussed with the sponsor before. • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × upper limit of normal (ULN) • Serum bilirubin = 1.5 × ULN with the following exception: o Patients with known Gilbert disease: direct serum bilirubin level = ULN for patients with total bilirubin Levels > 1.5 ULN. • Serum creatinine = 1.5 × ULN or Creatinine clearance = 30 mL/min (calculated using the Cockcroft-Gault formula) • Serum Albumin = 2.5 g/dL • International normalized ratio (INR) or activated Partial Thromboplastin Time (aPTT) = 1.5 × ULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose 9. Women of childbearing potential: • Should have a negative urine or serum pregnancy test within 14 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. • Agreement to remain abstinent (refrain from heterosexual intercourse) or use a non-hormonal contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 5 months after last study drug administration • A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a pos
Exclusion criteria
Exclusion criteria: 1. Evidence of metastatic disease (M1) 2. cT4b Stage 3. Prior treatment with immune checkpoint blockade therapies, 4. Treatment with investigational therapy within 28 days prior to initiation of study treatment 5. Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 4 weeks prior to initiation of study treatment 6. Bilateral pleural effusion 7. Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1, Cycle 1. 8. Treatment with a live-attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study, and for 5 months after the last dose of atezolizumab with or without tocilizumab 9. Treatment with systemic immuno-stimulatory agents within 4 weeks or five half-lives of the drug (whichever is longer) prior to initiation of study treatment 10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 11. Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment 12. Uncontrolled hypercalcemia 13. Uncontrolled tumor-related pain. 14. Uncontrolled diabetes mellitus 15. Pregnant and lactating women 16. Acute toxicities from previous therapy that have not resolved to Grade = 1, except for alopecia 17. Infections a. Positive human immunodeficiency virus (HIV) test: Known HIV+ patients may be included b. Active hepatitis B virus (HBV) infection (chronic or acute), positive HBsAg test at screening Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening followed by a negative HBV DNA test, are eligible for the study. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. c. Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test. d. Active tuberculosis e. Severe infection within 4 weeks prior to initiation of study treatment f. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment g. Patients receiving prophylactic antibiotics are eligible for the study. h. History of frequent severe diverticulitis. 18. Active or history of autoimmune disease or immune deficiency with the following exceptions: - Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study - Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study - Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible 19. Adverse events (AE) related to any previous radiotherapy, chemotherapy, targeted therapy or surgical procedure that have not reolved to Grade =1, except alopecia (any grade) and Grade 2 neuropathy 20. Prior allogeneic stem cell or solid organ transplantation 21. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computer tomography (CT) scan. History of radiation pneumonitis in the radi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Effect of atezolizumab with or without tocilizumab on tumorinfiltrating immune cells in resectable SCCHN • Feasibility of preoperative short time immunotherapy ;Secondary Objective: • Safety of preoperative short time immunotherapy and assessment of postoperative complication rates • To assess dynamics in tumor immunity • Exploratory analyses of predictive biomarker by gene and protein expression to establish correlation with pathological response • Characterization of changes in frequency and numbers of circulating immune cells • Resectability after immunotherapy • Influence of immunotherapy on histo-morphological assessment • (optional) set up of a registry for follow up of patients and subsequent documentation of relapse free survival (RFS) rate and overall survival (OS) rate;Primary end point(s): • Percentage of patients with at least 2-fold increase of GzmB+/CD8+ T cells by immunohistochemistry (IHC) after 1 administration of atezolizumab with or without tocilizumab between pre-treatment biopsy specimens and post-treatment resection specimens • Number of patients with completion of pre-operative immunotherapy and resection of SCCHN ;Timepoint(s) of evaluation of this end point: Analyses are based on pre- vs. post-treatment comparisons. An interim safety analysis is planned after 6 patients in each arm have been treated and undergone resection. An second interim safety analysis will be done if surgery is delayed for 3 weeks in the first 3 treated patients in each arm. The reasons for delay and the toxicity of the pre-operative immunotherapy will be critically reviewed by the SSMB. During this analysis the enrollment of further patients will be temprorally paused. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Assess effects of therapy on tumor-infiltrating immune cells, tumor tissue gene expression signatures, targeted pathways and blood immune cells by analysis of pre-treatment samples (biopsy and blood) versus tumor resection sample (tumor sample and blood). If available, blood and tumor material obtained at relapse will also be analyzed. Following variables will be assessed in each arm: 1. Safety of preoperative short time immunotherapy and assessment of postoperative complication rates 2. Safety and tolerability of preoperative immunotherapy 3. Safety of preoperative short time immunotherapy and assessment of postoperative complication rates ;Timepoint(s) of evaluation of this end point: Analyses are based on pre- vs. post-treatment comparisons. | — |
Countries
Germany
Contacts
Public ContactStudy Coordination
Universitätsmedizin Essen - Studienzentrum GmbH
Outcome results
None listed