E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic castration-resistant prostate cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic hormone-insensitive prostate cancer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 objective of this study is to determine the diagnostic accuracy of the primary PET measure, to predict clinical response in patients with mCRPC treated with cabazitaxel. |
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E.2.2 | Secondary objectives of the trial |
1) To determine the predictive value of alternative quantitative PET measures, including alternative standardized uptake values (SUV), metabolic volume, single lesion versus multiple lesion approach and interlesional concordance (heterogeneity) of PET signal changes.
2) To describe the toxic effects of cabazitaxel in terms of serious adverse events (with reference to CTCAE 4.03 criteria) irrespective of treatment relationship, of as well as cumulative administered cabazitaxel dose.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 years of age
2. Signed informed consent according to ICH-GCP before start of treatment and any study specific procedures
3. ECOG Performance Status 0-2
4. Histological or cytological confirmation of adenocarcinoma of the prostate.
5. Evidence of locally advanced disease, bone-, visceral and/or lymph node metastases on bone scan, CT-scan or MRI
6. Continued androgen deprivation therapy either by orchidectomy or GnRH agonist/antagonist
7. Serum testosterone level < 1.7 nmol/L (<50 ng/mL) within 21 days before treatment start
8. Disease progression occurring during or after completion of docetaxel treatment (+ADT) in hormone-sensitive setting or during or after completion of docetaxel treatment (as 1st line) in castration-resistant setting. Patients should have received adequate exposure to docetaxel, that is, not inferior to a cumulative dose of 225 mg/m². Disease progression to be defined as either (1) radiologic disease progression of osseous disease and/or of measurable lesions according to the Prostate Cancer Working Group 2 (PCWG2) criteria and/or (2) prostate-specific antigen progression according to the PCWG2 criteria and disease-related worsening of pain as judged by the treating physician.
9. Treatment with curative intent is not an option and patient has an indication for cabazitaxel as judged by the medical care provider.
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E.4 | Principal exclusion criteria |
1. Impossibility or unwillingness to take oral drugs
2. Geographical, psychological or other non-medical conditions interfering with follow-up
3. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection)
4. Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent
5. Chemotherapy or immunotherapy (other than LHRH analogues) within the last 4 weeks before study inclusion
6. Prior treatment with cabazitaxel, abiraterone, enzalutamide or radium-223 post-docetaxel.
7. History of severe hypersensitivity reaction (≥grade 3) to docetaxel
8. History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs.
9. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments)
10. Patients who have a concurrent yellow fever vaccination
11. Abnormal liver functions consisting of any of the following (within 21 days before start of treatment):
• Total bilirubin > 1 x ULN (except for patients with documented Gilbert’s disease);
• Alanine aminotransferase (ALAT/SGPT) and/or aspartate aminotransferase (ASAT/ALAT) > 1.5 x ULN
12. Abnormal hematological blood counts consisting of any of the following (within 21 days before start of treatment):
• Absolute neutrophil count < 1.5 x 109/L
• Platelets < 100 x 109/L
• Hemoglobin < 6.2 mmol/L (< 10.0 g/dL).
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E.5 End points |
E.5.1 | Primary end point(s) |
The main endpoint of this study is the diagnostic accuracy of the PET measures (as defined by PERCIST, using SUVidif with peak VOI) to predict clinical response at 3 and 6 months of treatment respectively, described as sensitivity, specificity, positive and negative predictive values, respectively. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 3 and 6 cycles after the start of cabazitaxel. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are:
- predictive value of changes of
o alternative standardized uptake values (as described by Verwer et al. [11])
o choline avid tumour volume (volume of lesion, defined using PET-based VOIs [17])
- impact of lesion selection on predictive value
o single lesion versus multiple lesion approach (according to PERCIST [7])
- interlesional concordance (heterogeneity) of PET signal changes
- serious adverse events (with reference to CTCAE 4.03 criteria) irrespective of treatment relationship
- cumulative administered dose of cabazitaxel
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 3 and 6 cycles after the start of cabazitaxel. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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 | No |
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.8.3 |
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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Last visit of the last subject. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |