Clinical trial NCT04622761: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: The Clatterbridge Cancer Centre NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Liverpool
First posted: 2020-11-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A two arm, phase II randomised multi-centre trial. 120 patients will be recruited to the trial. Patients will be randomised to a control arm of immediate surgery or a treatment arm in a ratio of 1:2 (control 40pts: treatment 80pts). Patients in the treatment arm will receive hormonal treatment and Cabazitaxel 25 mg/m2 day 1 intravenously over one hour every 21 days. Treatment will be continued for 4 cycles (3 months) unless disease progression, unacceptable toxicity or patient request.
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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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Primary outcomes:
measure: To assess the efficacy activity of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy in patients with high risk operable prostate cancer, measuring the reduction in treatment failure and comparing this to that obtained in the control arm
timeFrame: through study completion, average 3 years
Secondary outcomes:
measure: • To assess the efficacy of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy, measuring the pathological and radiological response rates and comparing this to that obtained in a control arm of immediate surgery.
timeFrame: 3 year follow up
measure: To assess the efficacy of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy, assessing surgical margin involvement and comparing this to that obtained in a control arm of immediate surgery.
timeFrame: 3 year follow up
measure: To assess the efficacy of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy, assessing lymph node involvement and comparing this to that obtained in a control arm of immediate surgery.
timeFrame: 3 year follow up
measure: To assess the efficacy of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy, measuring progression free survival and comparing this to that obtained in a control arm of immediate surgery.
timeFrame: 3 year follow up
measure: • To assess the efficacy of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy, measuring overall survival from time of randomisation to death and comparing this to that obtained in a control arm of immediate surgery.
timeFrame: 3 year follow up
measure: To assess the efficacy of neoadjuvant Cabazitaxel chemotherapy and hormonal therapy, measuring surgical feasibility and comparing this to that obtained in a control arm of immediate surgery.
timeFrame: 3 year follow up
measure: To assess the quality of life of patients receiving neoadjuvant Cabazitaxel chemotherapy and hormonal therapy and comparing this to quality of life patients in a control arm of immediate surgery using the EORTC QLQ-C30 version 3 questionnaire.
timeFrame: 3 year follow up
Other outcomes:
Locations:
Study officials:
References: