Phase II Study of the Use of Neoadjuvant Cabazitaxel With Hormonal Treatment in Patients Operable Prostate Cancer, Assess the Efficacy and Toxicity of Cabazitaxel, and Explore Potential Predictive and Prognostic Markers of Clinical Outcome

Phase II Study of the Use of Neoadjuvant Cabazitaxel With Hormonal Treatment in Patients With High Risk Operable Prostate Cancer, to Assess the Efficacy and Toxicity of Cabazitaxel, and, to Explore Potential Predictive and Prognostic Markers of Clinical Outcome

This study is evaluating the efficacy of cabazitaxel and hormonal treatment as neoadjuvant treatment for patients with clinically operable disease suitable for surgery, and a high risk of relapse after surgery

This study is evaluating the efficacy of cabazitaxel and hormonal treatment (LHRH analogues) as neoadjuvant treatment for patients with clinically operable disease suitable for surgery (no lymph node, visceral or bony metastases), and a high risk of relapse after surgery (5 year risk of relapse).

Patients will receive four cycles of neoadjuvant treatment (cabazitaxel treatment and 3 months LHRH treatment) unless there is evidence of disease progression, unacceptable toxicity or patient request to withdraw consent.

Inclusion Criteria:

1. Aged ≥18 years
2. ECOG performance status 0-1 (Appendix 2)
3. Diagnosis of high risk prostate cancer as defined by one or more of the following: clinically T2c/T3, Gleason 8-10 and or PSA >10ng/ml
4. Appropriate candidate for radical prostatectomy
5. Life expectancy greater than 10 years
6. Adequate organ function as evidenced by peripheral blood counts and serum chemistries at enrolment
7. Ability and capacity to consent and comply with study and follow-up procedures
8. Fit to receive chemotherapy

Exclusion Criteria:

1. Locally advanced or metastatic disease

2. Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer

3. Grade ≥2 peripheral neuropathy

4. Grade ≥2 stomatitis

5. History of severe hypersensitivity reaction (≥ grade 3) to taxane

6. History of severe hypersensitivity reaction (≥ grade 3) to polysorbate 80 containing drugs

7. Other concurrent serious illness or medical conditions

8. Inadequate organ and bone marrow function as evidenced by:

   1. Haemoglobin <10.0 g/dL
   2. Absolute neutrophil count <1.5 x 109/L
   3. Platelet count <100 x 109/L
   4. AST/SGOT and/or ALT/SGPT >1.5 xULN
   5. Total bilirubin >1.5 x ULN
   6. Serum creatinine >1.5 x ULN (if creatinine is 1.0 - 1.5 xULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60mL/min should be excluded - see Appendix 3)

9. Uncontrolled diabetes mellitus

10. Active uncontrolled gastro oesophageal reflux disease (GORD)

11. Active infection requiring systemic antibiotic or antifungal medication

12. Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment

13. 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 - see Appendix 5 for a list of CYP3A inhibitors)

14. 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) - see Appendix 4 for a list of CYP3A inducers)

15. Contraindications or sensitivity to GCSF treatments

16. History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.03), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g., pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.

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