Biomarker-based Study in R/M SCCHN
Biomarker-based Study in R/M SCCHN
This is a biomarker-driven trial that will enroll patients with recurrent or metastatic
 squamous cell carcinoma of the head and neck progressing after first-line platinum-based
 chemotherapy. Based on potential biomarkers and molecular alterations identified in the
 biopsy from the central platform, patients will be allocated in different cohorts. There will
 be biomarker-positive patient cohorts and immunotherapy cohorts.
General Inclusion Criteria:

 -  Histologically confirmed recurrent and/or metastatic SCCHN of the oral cavity,
 oropharynx, hypopharynx or larynx not amenable to curative treatment.

 -  At least one measurable lesion by MRI or CT-scan according to RECIST 1.1, evaluated
 within 2 weeks prior to registration. Such lesion must not have been previously
 irradiated; if the measurable lesion(s) have been irradiated, clear progression must
 be documented.

 -  Progressive disease after first line platinum-based chemotherapy with or without
 cetuximab given as palliative treatment or progressive disease within 1 year if
 platinum-based chemotherapy was given as a part of the multimodal curative treatment.
 Patients pre-treated with anti-PD1/anti-PDL1 are allowed.

 -  ECOG performance status 0 -1 with a life expectancy of at least 12 weeks.

 -  Tumor core biopsy from any accessible tumor at the recurrent or metastatic site
 available for central testing.

 -  Patients must have adequate organ function, evaluated within 14 days prior to cohort
 allocation:

 -  Hemoglobin ≥ 9 g/100 ml,

 -  Neutrophils ≥ 1,500/mm3,

 -  Platelets ≥ 100,000/mm3,

 -  Total bilirubin <1.5 times the upper limit of normal (ULN) (< 3 times the upper limit
 of normal for Gilbert's disease),

 -  Serum ALT and AST ≤ 2.5 x ULN,

 -  Adequate renal function measured by:

 -  Estimated creatinine clearance ≥45ml using Cockcroft and Gault formula or Creatinine ≤
 1.5 ULN

 -  International Normalized Ratio (INR) or Prothrombin Time (PT) must be within the
 normal ranges as per institution's standard. A window of 5% is allowed.

 -  Patients receiving anticoagulant therapy are allowed to participate as long as the
 PT/INR values are within the expected target range of their current dose.

 -  Clinically normal cardiac function based on -left ventricular ejection fraction (≥
 50%) as assessed either by multi-gated acquisition scan or cardiac ultrasound and 12
 lead ECG without clinically relevant abnormalities.

 -  Patients ≥ 18 years old and must be able to give written informed consent.

 -  Patients ≥ 70 years old must undergo the G8 screening.

 -  Women of child-bearing potential must have a negative pregnancy test (serum or urine
 within the 72 hours prior to cohort allocation).

 -  Patients of childbearing / reproductive potential must agree to use highly effective
 methods of contraception based on the Clinical Trial Facilitation Group (CTFG)
 guidance as of registration and up to 6 months after the last treatment dose. Highly
 effective methods can achieve failure rate of less than 1% per year when used
 consistently and correctly. Such methods include: For Women: combined (estrogen and
 progestogen containing) hormonal contraception associated with inhibition of ovulation
 (oral, intravaginal and transdermal), progestogen-only hormonal contraception
 associated with inhibition of ovulation (oral, injectable, implantable), intrauterine
 device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized
 partner and sexual abstinence. For Men: condoms, sexual abstinence (the reliability of
 sexual abstinence needs to be evaluated in relation to the duration of the clinical
 trial and the preferred and usual lifestyle of the patient) and no sperm donations
 during treatment and up to 6 months after last dose of treatment.

 -  Female subjects who are breast feeding should agree to discontinue nursing prior to
 the first dose of study treatment and up to 6 months after the last study treatment.

 -  Before patient registration/randomization, written informed consent must be given
 according to ICH/GCP, and national/local regulations.

 General Exclusion Criteria:

 -  Unresolved and significant toxicity CTCAE version 4.03 grade ≥ 2 from previous
 anticancer therapy other than alopecia.

 -  History of any of the following cardiovascular conditions within 6 months prior to
 registration:

 -  myocardial infarction,

 -  severe/unstable angina,

 -  ongoing cardiac dysrhythmias of CTCAE version 4.03 Grade 2 or more,

 -  atrial fibrillation of any grade,

 -  coronary/peripheral artery bypass graft,

 -  symptomatic congestive heart failure according to New York Heart Association (NYHA)
 Class III or Class IV,

 -  significant active cardiac disease including uncontrolled high blood pressure defined
 as systolic ≥150 and diastolic ≥100.

 -  cerebrovascular accident including transient ischemic attack

 -  thromboembolic events like symptomatic pulmonary embolism.

 -  Nasopharynx and sino-nasal tumor.

 -  Surgery or investigational drugs or chemotherapy or other anticancer therapy within 3
 weeks before cohort allocationor or for investigational drugs, within a time interval
 less than at least 5 half-lives of the investigational agent, whichever is shorter.
 Participant must have recovered from any surgical procedure. Curative radiation
 therapy (60-70 Gy) within 6 weeks of cohort allocation. Palliative radiation therapy
 (e.g. 8 Gy on a painful lesion) will be allowed.

 -  Known untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis.

 -  Known diagnosis of immune deficiency or a positive serology of Human Immunodeficiency
 Virus (HIV) (HIV 1/2 antibodies).

 -  Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative]
 is detected) or pre-existing liver cirrhosis.

 -  Known pre-existing interstitial lung disease (ILD). Bronchoemphysema is not considered
 as ILD.

 -  Other uncontrolled active illnesses or nonmalignant systemic disease (examples
 include, but are not limited to active infections requiring antibiotics, bleeding
 disorders, uncontrolled diabetes, uncontrolled ventricular arrhythmia, uncontrolled
 major seizure disorder, unstable spinal cord compression, superior vena cava syndrome
 …).

 -  Any psychiatric, psychological, familial, sociological or geographical condition
 potentially hampering compliance with the study protocol and follow-up schedule.

 -  Any malignancy (other than SCCHN, non-melanoma skin cancer or localized cervical
 cancer or localized and presumed cured prostatic cancer or basal cell carcinoma of the
 skin and carcinoma in situ of the cervix or bladder) within the last 3 years prior to
 treatment allocation.