High-Risk Cancer
Conditions
Keywords
untreated, high risk prostate cancer
Brief summary
This study is aimed at evaluating the efficacy regarding the response rate and metastasis-free survival time of cabazitaxel as a neoadjuvant treatment in patients with high risk prostate cancer.
Detailed description
Patients will be treated by 6 cycles of Cabazitaxel 25 mg/m2 every three weeks and extended radical prostatectomy and extended pelvic lymphadenectomy 4 weeks after completion of chemotherapy. Multiparametric MRI will be performed at baseline, after 3 cycles and after 6 cycles. If there will be evidence of clinical progression after 3rd cycle, patients can be removed from the study and given local therapy, including radical prostatectomy or external beam radiotherapy, at the discretion of the patient's physicians. If patients have evidence of response, they continue on treatment for a total of 6 cycles. If multiparametric MRI demonstrates stable disease an individual risk-benefit analysis has to be performed with regard to continuing or to stopping the neoadjuvant treatment since the definition stable disease includes patients with ≤ 20% tumour shrinkage or tumour progression
Interventions
DRUGCabazitaxel chemotherapy
given in 6 cycles
Sponsors
RWTH Aachen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Surgically resectable high risk prostate cancer with a 5-year relapse probability ≥ 60% according to the Kattan pre-operative nomogram (cancer 2009, 115: 1005-1010) * no prior therapy for prostate cancer such as androgen deprivation therapy, radiation therapy, or chemotherapy * ECOG performance status 0-1 * No evidence of active infection * Hemoglobin \>9.0 g/dL * Absolute neutrophil count \>1.5 x 109/L, * Platelet count \>100 x 109/L, * AST/SGOT and/or ALT/SGPT \<2.5 x ULN; * Total bilirubin \<1.0 x ULN, * Serum creatinine \<1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance \<60 mL/min should be excluded) * Patient information and signature of informed consent * Male ≥ 18 years * Patients of reproductive age must take appropriate contraceptive precautions during and for 6 months after the end of their participation in the study
Exclusion criteria
* Evidence of lymph node, visceral or bone metastases * previous major intrapelvic surgery * previous radiation therapy to the small pelvis * any type of malignancies within the last 5 years except basalioma and non-muscle invasive urothelial cancer of the urinary bladder * previous chemotherapy with taxanes (docetaxel, paclitaxel, cabazitaxel) for any indication * Hypersensitivity to the active substance or to any of the excipients * Known or suspected brain metastases or leptomeningeal metastases * Active or symptomatic viral hepatitis or chronic liver disease * Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete pathological response rate | 5 years | Primary endpoint: overall or cancer specific survival nor progression-free survival(PFS) in 5 years. Composite measurement. Key-parameters: * Complete pathohistological remission * Intra/perioperative compl. * PFS * Metastasis-FS * Biochemical, radiological, clinical PFS and androgen-deprivation FS * Objective progr. during cabazitaxel therapy (cab.th.) and post surgery * PSA response at the end of cab.th. * PSA progression after 12 w. of cab.th. * Percentage of pat. with undetectable PSA (\<0.1 ng/ml) post surgery * Relationship between PSA kinetics, histol. response and MRI response * Role of pathohistol. parameters such as intraductal, cribriform growth patterns and effect on response * Immunohistochemical evaluation of prostate biopsy and radical prostatectomy specimens of markers potentially associated with chemoresistance: growth differentiation factor 15, surviving, beta-tubuline I & II, p53, bcl-2, * Measurement of the serum concentrations of free circulating mDNA |
Countries
Germany
Outcome results
None listed