Clinical trial NCT03652233 (phase 1, status: withdrawn)
Conditions: recurrent squamous cell carcinoma of the head or neck, metastatic squamous cell carcinoma of the head or neck, squamous cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8, C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8, C44.520, C44.92, C44.02, C44.321, C44.521, C44.82, C44.42
Drugs: nivolumab, afatinib
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, CN(C)C\C=C\C(=O)NC1=C(O[C@H]2CCOC2)C=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1
Reason stopped: 
    low accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously
             treated with immunotherapy

          -  No prior immunotherapy for this disease, including therapies targeting PD-

             1, PD-L1, CTLA-4 or other cells and molecules aiming to modulate immune response
             against Squamous Cell Carcinoma of the Head and Neck.

          -  ECOG Performance Status of 0-1

          -  Normal organ and marrow function as defined below:

               -  WBC ≥ 2000 cells/μL

               -  Absolute neutrophil count (ANC) ≥ 1000 cells/μL

               -  Hemoglobin (Hgb) ≥ 9 g/dL

               -  Platelets ≥ 100,000/μL

               -  Estimated creatinine clearance ≥ 30 ml/min

               -  Left ventricular function with resting ejection fraction ≥ 50%

               -  Total bilirubin < 1.5 X ULN (Subjects with Gilbert's syndrome total bilirubin
                  must be ≤4 times institutional upper limit of normal)

               -  AST and ALT of < 2.5 X ULN

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to
             the start of Nivolumab. WOCBP must use appropriate method(s) of contraception. WOCBP
             should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time
             required for nivolumab to undergo five half-lives) after the last dose of
             investigational drug.

          -  Recovered from any previous therapy related toxicity to ≤ Grade 1 at study entry
             (except for stable sensory neuropathy ≤ Grade 2 and alopecia).

          -  Availability of a "newly obtained" standard of care biopsy obtained through either
             core or excisional biopsy. A newly obtained sample may be obtained up to 28 days prior
             to treatment initiation. Tissue beyond the 28-day window may be considered with the
             approval Protocol Chair. Tissue that has been previously irradiated or surgically
             intervened is acceptable

        Exclusion Criteria:

          -  Currently receiving any other investigational agents or using an investigational agent
             30 days prior to the first dose of trial treatment.

          -  Disease that is suitable for local therapy with curative intent.

          -  Untreated brain metastases/CNS disease excluded because of poor prognosis and because
             they often develop progressive neurologic dysfunction that would confound the
             evaluation of neurologic and other adverse events. Subjects with stable, treated CNS
             metastases are eligible.

          -  Known hypersensitivity to afatinib or nivolumab.

          -  Prior EGFR-targeted small molecule therapy except cetuximab.

          -  Hormonal therapy with the exception of those used for diabetes or birth control is not
             allowed.

          -  Radiotherapy within 4 weeks prior to randomization, except as follows:

        Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior
        to randomisation, and Single dose palliative treatment for symptomatic metastasis outside
        above allowance to be discussed with sponsor prior to enrolling.

          -  Major surgery within 4 weeks before starting study treatment or scheduled for surgery
             during the projected course of the study.

          -  History or presence of clinically relevant cardiovascular abnormalities such as
             uncontrolled hypertension (systolic blood pressure ≥ 160 or diastolic blood pressure ≥
             90), congestive heart failure NYHA classification of ≥ 3, unstable angina or poorly
             controlled arrhythmia as determined by the investigator. Myocardial infarction within
             6 months prior to the enrollment.

          -  Previous or concomitant malignancies at other sites, except effectively treated
             non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ
             or effectively treated malignancy that has been in remission for more than 3 years and
             is considered to be cured.

          -  Requiring treatment with any of the prohibited concomitant medications listed in
             section 6.4 that cannot be stopped for the duration of trial participation.

          -  Known active or pre-existing interstitial lung disease.

          -  Any history or presence of poorly controlled gastrointestinal disorders that could
             affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis,
             chronic diarrhea and malabsorption).

          -  Prior immune checkpoint targeted therapy, including anti-PD-1, anti-PD-L1 or
             anti-PD-L2.

          -  History of autoimmune disease or disease requiring immunosuppression therapy.

          -  Uncontrolled inter-current illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Women must not be breastfeeding.

          -  Men who are sexually active with WOCBP must use any contraceptive method (Appendix II)
             with a failure rate of less than 1% per year Men receiving nivolumab and who are
             sexually active with WOCBP will be instructed to adhere to contraception for a period
             of 31 weeks after the last dose of investigational product Women who are not of
             childbearing potential (i.e., who are postmenopausal or surgically sterile as well as
             azoospermic men do not require contraception.

          -  Testing positive Human Immunodeficiency Virus (HIV) acquired immunodeficiency syndrome
             (AIDS).

          -  Active hepatitis B or hepatitis C.

          -  Active infection requiring systemic antibiotic treatment or intensive care.

          -  Active non-infectious pneumonitis

          -  Received live vaccine within 30 days of start of study treatment.

          -  Known psychiatric or substance abuse disorders that may interfere with cooperation
             with the requirements of the trial.

          -  Other significant medical conditions that may interfere with surgical biopsy and
             afatinib and nivolumab administration.