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

Prostate Cancer Clinical Trial

— CHROME  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04622761
• Other study ID #: RDD630
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 15, 2021
• Est. completion date: May 2, 2026

Study information

• Verified date: November 2020
• Source: The Clatterbridge Cancer Centre NHS Foundation Trust
• Contact: Marie Maguire
• Phone: 0151 556 5321
• Email: maria.maguire2[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: May 2, 2026
• Est. primary completion date: November 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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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Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Cabazitaxel
Patients will receive Cabazitaxel 25 mg/m2 * intravenously over one hour every 21 days (on Day 1 of each cycle). Treatment will be continued for 4 cycles unless disease progression, unacceptable toxicity or patient request. These patients will have surgery (radical prostatectomy) 4-86 weeks following treatment. *Cabazitaxel dose should be capped at 50mg (BSA=2)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
The Clatterbridge Cancer Centre NHS Foundation Trust	University of Liverpool

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Treatment failure is defined as: PSA level = 0.12ng/ml measured on at least two occasions (1 confirmatory sample) post-surgery within three years of follow-up or death related to prostate cancer or use of a salvage therapy or not undergoing surgery at all.)	through study completion, average 3 years
Secondary	• 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.	Pathological response rate assessed as per pTNM staging system Radiological response rates as defined in RECIST V1.1 Combined to give overall response rate	3 year follow up
Secondary	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.	The proportion of patients with positive resection margin will be reported and compared across the treatment groups using Chi-square tests. Multivariable models using logistic regression techniques shall be used to adjust for key prognostic variables of interest.	3 year follow up
Secondary	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.	The proportion of patients with positive lymph nodes will be reported and compared across the treatment groups using Chi-square tests.	3 year follow up
Secondary	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.		3 year follow up
Secondary	• 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.		3 year follow up
Secondary	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.	The proportion of patients with delays to surgery, perioperative morbidities, mortalities and surgical complications will be reported and compared across the treatment groups.	3 year follow up
Secondary	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.	Responses to EORTC QLQ-C30 will be reported (median, IQR) according to global health status, the functional scales and symptom scales, by intervention group, and over time. Joint modelling or quality-adjusted survival analysis will be undertaken to allow a simultaneous assessment of quality of life and survival.	3 year follow up