Randomized Phase II Study of CABAZITAXEL versus METHOTREXATE in patients with recurrent or metastatic squamous cell carcinoma of the head and neck previously treated with platinum-based therapy.

Study Objective

To evaluate the efficacy of Cabazitaxel in patients with palliative squamous cell carcinoma of the head and neck previously treated with platinum-based therapy.

Participation conditions

Inclusion criteria

• Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to curative treatment with surgery and/or chemotherapy and/or radiation
• At least one measurable lesion by MRI or CT-scan according to RECIST 1.1
• Progressive disease after first line platinum-based chemotherapy given as palliative treatment or progressive disease within one year if platinum-based chemotherapy was given as a part of the multimodal curative treatment
• ECOG performance status 0 -2, in stable medical condition
• Patients must have an expected survival of at least 3 months
• Paraffin-embedded tumor tissue available for immunohistochemistry but not mandatory
• Patients must be over 18 years old and must be able to give written informed consent
• Women of child-bearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to enrollment)
• Patients must have adequate organ function (Hemoglobin ≥ 9 g/100 ml, Neutrophils ≥ 1,500/mm3, Platelets ≥ 100,000/mm3,  total bilirubin < 1 time the upper limit of normal (ULN) for age, serum alanine aminotransferase (ALT) < 1.5  ULN  for age, aspartate aminotransferase (AST) < 1.5   ULN for age , serum creatinine 1.5 x ULN for age                                 
• Signed informed consent prior to beginning protocol specific procedure
• Sexually active patients must use effective contraception during the period of therapy and up to 150 days after the last treatment dose.  Acceptable contraception includes, but is not limited to: oral hormone therapy, partner vasectomy, or double barrier contraception (which is defined as a male condom plus spermicide in combination with either a female condom, or diaphragm, or cervical cap or intrauterine device)

Exclusion criteria

• Non-squamous head and neck cancer
• Nasopharynx cancer
• More than two lines of chemotherapy for palliative treatment
• Surgery or investigational drugs or chemotherapy within 4 weeks before study inclusion. Curative radiation therapy (60-70 Gy) within 8 weeks. For palliative radiation therapy (i.e  8 Gy on a painful lesion), no delay is needed
• Previous treatment with Cabazitaxel
• Significant active cardiac disease including: uncontrolled high blood pressure according to the CTCAE 4.03 grading, unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias
• Other uncontrolled illnesses (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes …)
• Previous malignancy from which the patient has been disease-free for < 5years, as other than SCCHN
• Previous treatments with Taxanes and/or anti-EGFR therapy are not an exclusion criteria.
• Active grade > 2 peripheral neuropathy
• Active grade > 2 stomatitis
• Known brain or leptomeningeal involvement
• History of severe hypersensitivity reaction (> grade 3) to polysorbate 80 containing drugs
• Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A/5. A one-week washout period is necessary for patients who are already on these treatments
• Organic brain syndrome or significant psychiatric abnormality that would preclude participation in the full protocol and follow up
 

Centre Hospitalier de Luxembourg