A Phase II, Open-Label, Multicenter Trial of Cabazitaxel in Patients With Recurrent or Metastatic Head and Neck Cancer After Failure Of Cisplatin, Cetuximab and Taxanes

Patients will be treated with intravenous cabazitaxel 25 mg/m2 every 3 weeks (D1=D22) for 6 cycles.

In absence of progression disease or unacceptable toxicity, the treatment could be continued until a maximum of 10 cycles.

Disease response will be assessed every 6 weeks (i.e. every 2 cycles) clinically and by CT-scan.

An interim analysis will be carried out after the inclusion of the first 10 eligible and assessable patients.

Inclusion criteria

• Metastatic or recurrent Head and neck cancer
• Progression after cisplatin, cetuximab and taxanes (drugs could have been administered alone or in combination) given for recurrent/metastatic disease
• Age ≥ 18
• ECOG performance status ≤ 2
• At least one measurable lesion on CT-scan (as per RECIST criteria V1.1).
• Life expectancy ≥ 3 months
• Adequate hematologic function (neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L; Hb ≥ 9.0 g/dL), renal function (clearance creatinine using the CKD-EPI formula (Chronic Kidney Disease Epidemiology group) ≥ 60 mL/min) and hepatic function (serum bilirubin ≤ 1 ULN; AST and ALT ≤ 2.5 x ULN).
• Potentially reproductive patients must agree to use an effective contraceptive method while on treatment, beginning 2 weeks before the first dose of investigational product and for 6 months after the final dose of investigational product.
• Women of childbearing potential must have a negative serum beta-HCG pregnancy test within 14 days prior of enrolment and/or urine pregnancy test within 48 hours before the first administration of the study treatment.
• Patients must be affiliated to a Social Security System.
• Patient who have received the information sheet and signed the informed consent form.
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion criteria

• Active concurrent malignancy
• Progression in the 3 months after the completion of treatment for localized disease
• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as :

• infection,
• cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, LVEF > grade 2,
• current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment),
• renal disease,
• active GI tract ulceration, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded,
• severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air).
• Patients must have recovered of previous toxicity of chemotherapy and must not have toxicity grade > 1 ; grade ≥ 2 for neuropathy and grade ≥ 2 for cutaneous rash after cetuximab (in the CTCAE v4.0)
• Hypersensitivity to cabazitaxel, to other taxanes, or to any excipients of the formulation including polysorbate 80
• Pregnant women, women who are likely to become pregnant or are breast-feeding.
• Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Patients who received any other investigational drugs within the 14 days prior to the start of cabazitaxel.
• Patients receiving radiation within 4 weeks prior to the first dose of study drug.
• Patients already included in another therapeutic trial involving an experimental drug
• Individual deprived of liberty or placed under the authority of a tutor.
• Other primary tumors within the previous 3 years
• Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5. A one week wash-out period is necessary for patients who are already on these treatments.