Squamous cell carcinomas of the head and neck (SCCHN) Squamous cell carcinomas of the head and neck (SCCHN)
Conditions
Interventions
There will be 3 treatment phases in this study:
* Lead-in Phase: On Day 1 of the Lead-in Phase of the study, patients will
receive a single dose of avelumab or matching placebo, administered 7 days
* CRT Phase: Avelumab or matching placebo will be administered on Days 8, 25,
and 39 in conjunction with SOC CRT starting on Day 1 of the CRT phase
* Maintenance Phase: Following completion of the CRT Phase, avelumab or
matching placebo will be administered every 2 weeks (Q2W) for 12 months during
the Maintenance Phase.
avelumab
Head and neck cancer
randomized
Sponsors
Pfizer
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with tissue available. 2. High-risk disease as defined by: * HPV negative disease, Stage III, IVa, IVb per tumor/nodes/metastasis (TNM) guidelines for head and neck sites (American Joint Committee on Cancer [AJCC] 7th Edition); or * Non oropharyngeal HPV positive disease, Stage III, IVa, IVb per TNM guidelines for head and neck sites (AJCC 7th Edition); or * HPV positive oropharyngeal disease T4, N2c, or N3 per TNM guidelines for head and neck sites (AJCC 7th Edition); * where HPV status will be determined per institutional standard using p16 immunohistochemistry (IHC). 3. No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative intent. 4. Available tumor samples for submission or willing to undergo further tumor biopsies: * Availability of a formalin-fixed paraffin-embedded (FFPE) tumor tissue block from primary tumor or nodal biopsy. If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable. 5. Age *18 years (*20 years in Japan). 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 7. Adequate bone marrow function, including: * Absolute Neutrophil Count (ANC) *1,800/µL or *1.8 x 10E9/L. * Platelets *100,000/µL or *100 x 10E9/L. * Hemoglobin *9 g/dL (may have been transfused). 8. Adequate renal function, including: * Estimated creatinine clearance *50 mL/min as calculated using the Cockcroft Gault (CG) equation. 9. Adequate liver function, including: * Total serum bilirubin *1.5 x upper limit of normal (ULN). * Aspartate and alanine aminotransferase (AST and ALT) *2.5 x ULN. 10. Pregnancy test (for patients of childbearing potential) negative at screening. 11. Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later). Female patients who are not of childbearing potential (ie, meet at least one of the following criteria): a. Have undergone a documented hysterectomy and/or bilateral oophorectomy; or b) Have medically confirmed ovarian failure; or Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state. 12. Evidence of a signed and dated informed consent document indicating that the patient (or a legally acceptable representative, as allowed by local guideline/practice) has been informed of all pertinent aspects of the study. 13.Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion criteria
Exclusion criteria: 1. Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways. 2. Major surgery * 4 weeks prior to randomization. 3. Diagnosis of any other malignancy within 5 years prior to randomization, except for superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score *6) either curatively treated or deemed to not require treatment, ductal in situ carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder. 4. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. 5. Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. 6. Active infection requiring systemic therapy. 7. Known prior severe hypersensitivity to investigational products or any component in the formulations, including known severe hypersensitivity reactions to mAbs, cisplatin, or platinum-related compounds (NCI CTCAE v4.03 Grade * 3). 8. Use of immunosuppressive medication at time of randomization, except the following: a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses *10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 9. Prior organ transplantation including allogenic stem-cell transplantation. 10. Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. 11. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA [ribonucleic acid] if anti-HCV antibody screening test positive). 12. Vaccination within 4 weeks prior to randomization except for administration of inactivated vaccines. 13. Current use of or anticipated need for treatment with other anti-cancer drugs. 14. Pregnant female patients, breastfeeding female patients, and male patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later). 15. Other severe acute or chronic medical conditions including: colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (see Appendix 3 for specific modifications, including pathologic confirmation) by investigator assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| * OS. * Antitumor Activity: Pathologic complete response in any resected specimens, neck dissection. * Antitumor Activity: Locoregional failure, objective response, distant metastatic failure, and duration of response, per modified RECIST v1.1 (Appendix 3) by investigator assessment. * Safety: Adverse events and laboratory abnormalities as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03; vital signs (blood pressure, pulse rate). * Pharmacokinetics: * Maximum concentrations (Cmax) and trough concentrations (Ctrough) for avelumab. * Area under the concentration-time curve extrapolated to infinity (AUCinf), Cmax, clearance (CL), time to maximum plasma concentration (Tmax), elimination half-life (t1/2), and volume of distribution (Vz) for cisplatin (total and free), as data permit. * Immunogenicity: Incidence of ADA (neutralizing antibody) against avelumab. * Patient-Reported Outcomes: Disease-related symptoms and Health-Related Quality of Life as measured by the National Cancer Comprehensive Network (NCCN) Head and Neck Symptom Index-22 items (FHNSI-22), and the EuroQoL Group 5-Dimension 5 Level Self-Report Questionnaire (EQ-5D-5L). * Biomarkers: Tumor tissue biomarkers including, but not limited to, PD-L1 expression and tumor-infiltrating CD8+ T-lymphocytes. | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Greece, Israel, Italy, Japan, Korea (the Republic of), Netherlands, Poland, Russian Federation, Spain, Switzerland, Taiwan (Province of China), United Kingdom, United States of America
Outcome results
None listed