Nivolumab in Recurrent or Metastatic Salivary Gland Carcinoma of the Head and Neck

A Phase II, Multicenter, Non Randomized, Open Label Study of Nivolumab In Recurrent and/or Metastatic Salivary Gland Carcinoma of the Head and Neck

INDICATION:

Patients with recurrent and/or metastatic salivary glands carcinoma who have progressed during the 6 months period before entering the study and who are eligible for nivolumab monotherapy.

METHODOLOGY:

The present study is a multicenter, open-label, non-controlled, phase II study in patients who are suffering from recurrent and/or metastatic Salivary Glands Carcinoma, who have progressed during the 6 months period before entering the study and who are eligible for nivolumab monotherapy.

All eligible patients will receive nivolumab treatment for a maximum of 12 cycles of treatment. 92 eligible patients will be dosed with nivolumab intravenously over 60 minutes (± 5 minutes) at 3 mg/kg every two weeks.

Each 28-day dosing period will constitute a cycle.

Inclusion Criteria:

• Adult men and women ≥18 years
• Histologically confirmed carcinoma of the salivary glands, recurrent or metastatic (adenoid cystic carcinoma or non-adenoid cystic carcinoma) not eligible to local treatment
• Pre-treatment tumor tissue available for central review and biomarkers analysis.
• At least one measurable lesion ≥10 mm (outside any previous irradiated field) according to RECIST v1.1 with magnetic resonance imaging (MRI) or computed tomography (CT)-scan
• Patients with confirmed disease progression at study entry. The "baseline" radiological evaluation (either MRI or CT scan) should demonstrate disease progression by RECIST 1.1 when compared to a prior disease assessment done within a 6 months period prior to screening
• Previous anti-cancer therapies must be discontinued at least 4 weeks prior to administration of study drug. Concomitant, palliative (limited-field) radiation therapy is permitted during the study, if all of the following criteria are met: (1) repeated imaging demonstrates no new sites of bone metastases ; (2) The lesion being considered for palliative radiation is not a target lesion
• Performance status Eastern Cooperative Oncology Group (ECOG) <2
• Screening laboratory values must meet the following criteria and should be obtained within 7 days prior to starting study drug: White Blood Cell (WBC) ≥2000/mm³, Neutrophils ≥1500/mm³, Platelets ≥100 000 /mm³, Hemoglobin >9.0 g/dL, Serum creatinine ≤1.5 x Upper Limit of Normal (ULN) or creatinine clearance (CrCl) ≥40 mL/min (using the Cockcroft-Gault formula), aspartate transaminase (AST) / alanine transaminase (ALT) / alkaline phosphatase (PAL) ≤3 x ULN or ≤5 x ULN when liver metastases, Total Bilirubin ≤1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL)
• Women of childbearing potential (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
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
• Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose
• Men who are sexually active with WOCBP must use any contraceptive method 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 (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception)
• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
• Patients with social insurance coverage

Exclusion Criteria:

• Stable disease
• Symptomatic / active brain metastases
• Immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. A 2 weeks wash-out minimum is required before starting study drug
• Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Patients with any active or suspected autoimmune disease or an history of known autoimmune disease (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are however eligible for this trial)
• Patients having received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• History of organ transplantation requiring long-term immunosuppressive medications
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Known history or active tuberculosis
• Any other malignancy (except for appropriately treated superficial basal cell skin cancer and surgically cured in situ cancer) unless free of disease for at least three years
• History of allergy to study drug components
• Any toxicity (other than alopecia) attributed to prior anti-cancer therapy not resolved to grade 1 (NCI CTCAE version 4) at baseline level before administration of study drug.
• Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake (if applicable)
• Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study
• Individuals deprived of liberty or placed under the authority of a tutor
• Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment and during the treatment period