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

Study Overview
=================
Brief Summary
-----------------
An evaluation of the activity of cabazitaxel chemotherapy in relapsed cancer of the penis. Safety and tolerability will be monitored and survival will be assessed. It is hypothesised that cabazitaxel is useful in increasing progression free survival in relapsed penile cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Trial of Cabazitaxel Chemotherapy in Relapsed Locally Advanced &/or Metastatic Carcinoma of the Penis

Conditions
-----------------
Penile Neoplasm

Intervention / Treatment
-----------------
* Drug: Cabazitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabazitaxel<br>Six cycles of chemotherapy comprising: Cabazitaxel 25mg/m2 to be repeated at intervals of 21 days | Drug: Cabazitaxel<br>* Six cycles of chemotherapy comprising: Cabazitaxel 25mg/m2 to be repeated at intervals of 21 days.<br>* Other names: Jetvana;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | Complete response recorded from the start of the treatment to completion of 6 cy-cles of treatment determined by radiological response assessment | 18 weeks | 
| Partial response | Partial response recorded from the start of the treatment to completion of 6 cy-cles of treatment determined by radiological response assessment | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival defined as the time from registration to the first of one of the following: development of radiological disease progression (RECIST 1.1) or death from any cause | Until patient progresses, which is approximately 6 weeks after randomisation | 
| Overall survival | Overall survival defined as time from registration to the date of death due to from any cause | Until patient dies, which is approximately 3 months after randomisation | 
| Acute toxicity (Defined by number of CTCAE v4.03 Adverse Events, Adverse Reactions and by grades and the worst grade). | Acute toxicity (Defined by number of CTCAE v4.03 Adverse Events, Adverse reactions and by grades experienced by the patient collected at study visits and recorded on an Adverse Event Case report form. . | After each cycle (every 3 weeks) for maximally 6 cycles therefore 18 weeks whilst on treatment and at the 3 month visit timepoint | 
| Late toxicity (Defined by number of CTCAE v4.03 Adverse Events, Adverse Reactions and by grades and the worst grade). | Late toxicity (Defined by number of CTCAE v4.03 Adverse Events, Adverse reactions and by grades experienced by the patient collected at study visits and recorded on an Adverse Event Case report form. . | From 3 months post treatment Cycle 1 Day 1 to up to 6 months recorded at the 3 month and 6 month timepoint. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Recurrent, Locally advanced, Metastatic