E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
high-risk prostata cancer patients |
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E.1.1.1 | Medical condition in easily understood language |
patients with untreated, high-risk localized prostate cancer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary goal of this trial is to define the pathologic complete response rate of cabazitaxel chemotherapy in patients with untreated, high-risk localized prostate cancer. |
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E.2.2 | Secondary objectives of the trial |
- intra & perioperative compl. - cabazitaxel associated side effects according NCI-CTC-AE version 4.3 - Overall progression-free survival (PFS) - Metastasis-free surv. - Biochemical, radiological, clinical PFS & androgen-deprivation free survival - Object. progr. during cabazitaxel th. & post surg. - PSA response a.t.end of cabazitaxel th. - PSA progr. after 12 w of cabazit. th. - Percentage of pat.with undetectable PSA (<0.1 ng/ml) after surgery - role of pathohistol. param. such as intraductal, cribriform growth patterns and their effect on response - immunohistochemicl. eval. of prostate biopsy (taken 2 to 6 weeks before surgery) and radical prostatectomy specimens of markers potentially associated with chemoresistance: growth differentiation factor 15, surviving, beta-tubuline I & II & III, p53, bcl-2 - measurement of the serum conc. of free circulating mitochondrial DNA (blood samples will be drawn prior each chemoth. admin., prior to surgery and 1 w after surgery)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this trial is to define the pathologic complete response rate of cabazitaxel chemotherapy in patients with untreated, high-risk localized prostate cancer. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• intra- and perioperative complications • Overall progression-free survival (PFS) • Metastasis-free survival • Biochemical, radiological, clinical PFS and androgen-deprivation free survival • Objective progression during cabazitaxel therapy and after surgery • PSA response at the end of cabazitaxel therapy • PSA progression after 12 weeks of cabazitaxel therapy • Percentage of patients with undetectable PSA (<0.1 ng/ml) after surgery • Relationship between PSA kinetics, histological response and MRI response • role of pathohistological parameters such as intraductal, cribriform groth patterns and their 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 mitochondrial DNA • Toxicity (cabazitaxel associated adverse reactions) will be recorded using the NCI-CTCAE (v4.3), evaluation of surgery related complications according to the Clavien classification.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |