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

NCT04622761 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RDD630
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• • 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.

  3 year follow up

• 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.

  3 year follow up

• 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.

  3 year follow up

• 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

• • 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

Study Arms (2)

control

NO INTERVENTION

Immediate surgery (radical prostatectomy) (standard care)

treatment

EXPERIMENTAL

14 days prior to starting Cabazitaxel patients will take 50mg Bicalutamide once daily for 21 days. 7 days prior to starting Cabazitaxel patients will be given 3 months LHRH treatment via injection. The entire dose will be administered via one injection 7 days prior to starting Cabazitaxel. This may be either leuprorelin or goserelin acetate and should be given as per local practice. At least 30 minutes prior to each administration of Cabazitaxel, patients will be administered IV premedication consisting of: 50mg Ranitidine 10mg Chlorphenamine 8mg Dexamethasone Daily from Day 1 until end of Cabazitaxel treatment patients will take 10mg Prednisolone once daily from Day 1 until end of Cabazitaxel treatment Day 1 of each cycle - 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.

Drug: Cabazitaxel

Interventions

Cabazitaxel DRUG

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)

Also known as: jevtana, XRP6258, RPR116258A

treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years
• ECOG performance status 0-1 (Appendix 2)
• 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
• Appropriate candidate for radical prostatectomy
• Life expectancy greater than 10 years
• Adequate organ function as evidenced by peripheral blood counts and serum chemistries at enrolment
• Ability and capacity to consent and comply with study and follow-up procedures
• Fit to receive chemotherapy

You may not qualify if:

• Locally advanced or metastatic disease
• Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer
• Grade ≥2 peripheral neuropathy
• Grade ≥2 stomatitis
• History of severe hypersensitivity reaction (≥ grade 3) to taxane
• History of severe hypersensitivity reaction (≥ grade 3) to polysorbate 80 containing drugs
• Other concurrent serious illness or medical conditions
• Inadequate organ and bone marrow function as evidenced by:
• Haemoglobin \<10.0 g/dL
• Absolute neutrophil count \<1.5 x 109/L
• Platelet count \<100 x 109/L
• AST/SGOT and/or ALT/SGPT \>1.5 xULN
• Total bilirubin \>1.5 x ULN
• 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)
• Uncontrolled diabetes mellitus

Sponsors & Collaborators

• The Clatterbridge Cancer Centre NHS Foundation Trust: lead
• University of Liverpool: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; XRP6258

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

Marie Maguire

CONTACT

0151 556 5321; maria.maguire2@nhs.net

Claire Taylor

CONTACT

0151 795 14010; chrome@liverpool.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: November 10, 2020
• Study Start: January 15, 2021
• Primary Completion: November 2, 2025
• Study Completion: May 2, 2026
• Last Updated: January 5, 2021

Record last verified: 2020-11