recurrent or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) progressing after prior platinum-based therapy (radiochemo-therapy or systemic chemotherapy) MedDRA version: 20.0 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: 20.0 Level: PT Classification code 10071540 Term: Head and neck cancer metastatic System Organ Class:
Conditions
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 2. Age = 18 years at time of study entry 3. Histological or cytological confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) or nasal sinus not amenable to local therapies 4. Availability of tumor tissue from biopsy for determination of PD-L1 and HPV status according to the following priority ranking: i) recent biopsy (=3 months old) without intervening therapy; ii) any recent biopsy (=3 months old); iii) any archival tumor tissue (> 3 months old) [Biopsy should be excisional, incisional or core biopsy. Fine needle aspiration is not allowed.] 5. Progression or recurrence during or after platinum-based palliative chemotherapy for relapsed or metastatic disease OR progression within 6 months after completion of definitive platinum-containing radiochemotherapy for locally advanced disease 6. At least 1 measurable lesion according to RECIST 1.1 7. ECOG performance status 0-1 8. Completion of local therapy for brain metastases with discontinuation of steroids prior to start of study treatment 9. Adequate blood count, liver-enzymes, and renal function: • neutrophil count > 1.5 x 10^6/mL • platelet count = 100 x 10^9/L (>100,000 per mm^3) • hemoglobin = 9 g/dL • INR = 1.5 and aPTT = 1.5 x ULN during the last 7 days before therapy • AST (SGOT)/ALT (SGPT) =65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
Exclusion criteria: Medical criteria: 1. Nasopharynx carcinoma or carcinoma of salivary glands 2. Life expectancy less than 3 months 3. Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to: a) Minor surgery = 24 hours prior first dose of nivolumab monotherapy b) Anticancer treatment during the last 30 days prior to start of nivolumab-monotherapy treatment, including systemic therapy, or major surgery [palliative radiotherapy has to be completed at least 2 weeks prior to start of study treatment] c) Known active HBV, HCV or HIV infection d) Active tuberculosis e) Any other active infection requiring systemic therapy f) History of allogeneic tissue/solid organ transplant (including hematopoetic stem cell transplantation) g) Diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of nivolumab-monotherapy or randomization. h) Has an active autoimmune disease requiring systemic treatment within the past 3 months before enrollment or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study. Psoriasis not requiring treatment is not excluded from the study. i) Live vaccine within 30 days prior to the first dose of nivolumab-monotherapy treatment or during study treatment. j) Other active malignancy requiring treatment k) Clinically significant or symptomatic cardiovascular/cerebrovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before enrollment l) History or clinical evidence of CNS metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of nivolumab-monotherapy treament. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases Drug related criteria: 4. Medication that is known to interfere with any of the agents applied in the trial. 5. Has known hypersensitivity to nivolumab or ipilimumab or docetaxel or any of the constituents of the products. 6. Any other efficacious cancer treatment except protocol specified treatment at study start. Safety criteria: 7. Patient has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. [Subjects with = Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.] 8. Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to test whether dual checkpoint blockade is superior to docetaxel chemotherapy as early salvage therapy in R/M-SCCHN.;Secondary Objective: to assess efficacy, feasibility and safety of an intensified immunotherapy regimen;Primary end point(s): Objective response rate in all randomized patients;Timepoint(s) of evaluation of this end point: End of Study (EoS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • OS (measured from beginning of nivolumab-monotherapy therapy and from randomization; including sub-group analysis for HPV status; PD-L1 expression and tumor localization (i.e. oropharynx carcinoma)) • PFS (measured from beginning of nivolumab-monotherapy and from randomization; including sub-group analysis for HPV status; PD-L1 expression and tumor localization (i.e. oropharynx carcinoma)) • BOR, DOR • QoL (EORTC QLQC30; HN35; EQ-5D) • AEs/SAEs;Timepoint(s) of evaluation of this end point: End of Study (EoS) | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed