A Trial of Cabazitaxel Chemotherapy in Relapsed Locally Advanced &/or Metastatic Carcinoma of the Penis

First line treatment of penile cancer often combines Docetaxel, Cisplatin and 5Fluouracil (5FU) and there is currently no United Kingdom standard second line agent. Carbazitaxel has been shown to kill both taxane resistant and sensitive cells. JAVA-P is a phase two, single arm study of the use of carbazitaxel for relapsed, locally advanced or metastatic carcinoma of the penis. Seventeen patients will be recruited over two years, with adverse events and progression free survival being assessed. Results may indicate the need for larger studies to evaluate carbazitaxel as a first line agent.

Inclusion criteria

• Histologically-proven squamous cell carcinoma of the penis
• Performance status ECOG 0-2
• Written informed consent
• Measurable disease as per RECIST 1.1
• Fit to receive cabazitaxel as second line chemotherapy
• Previously received TPF or cisplatin-5FU as first line systemic chemotherapy for penile cancer
• Adequate organ function as evidenced by the following peripheral blood counts and serum biochemistry at enrollment:

• Neutrophils ≥1.5 x 109/L
• Haemoglobin ≥10 g/dL
• Platelets ≥100 x 109/L
• Total bilirubin <1.5 upper limit of normal (ULN)
• Alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤1.5 x ULN
• Serum creatinine ≤1.5 x ULN. (If creatinine is 1.0-1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with a creatinine clearance <60 ml/min should be excluded.)

Exclusion criteria

• Pure veruccous carcinoma of the penis
• Squamous carcinoma of the urethra
• T1 N1 M0 disease
• T2 N1 M0 disease
• Unfit for this regimen (as assessed by the multidisciplinary team)
• Contraindication to chemotherapy
• ECOG Performance Status > 2
• Active Grade ≥2 peripheral neuropathy
• Active secondary cancers
• Other concurrent serious illness or medical conditions
• Electrocardiogram (ECG) evidence of uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension, history of congestive heart failure, or myocardial infarction within last 6 months.
• Uncontrolled diabetes mellitus.
• History of severe hypersensitivity reaction (≥grade 3) to docetaxel
• History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
• Active infection requiring systemic antibiotic or anti-fungal medication
• Participation in another clinical trial with any investigational drug within 30 days prior to study registration.
• Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A4/5. A 1-week washout period is necessary for patients who are already on these treatments.
• Concurrent or planned treatment with strong inducers of cytochrome P450 3A4/5. A 1-week washout period is necessary for patients who are already on these treatments.