E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed, locally advanced and/or metastatic carcinoma of the penis. |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the penis which has spread to other areas of the body. |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007384 |
E.1.2 | Term | Carcinoma in situ of penis |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the activity of Cabazitaxel chemotherapy in relapsed cancer of the penis as assessed by objective response rate. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of Cabazitaxel To assess prgression free survival To assess overall survival To evaluate the frequency, severity and relatedness of any adverse events To asess acute toxicity To asess late toxicity To asess quality of life
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent Male ≥ 18 years Histologically proven squamous cell carcinoma of the penis Stage: M1 or M0 Tx N3 or M0 Tx N2 and deemed inoperable by MDT or M0 T3 N1 or M0 T4 any N ECOG ≤2 Previous frist line chemotherapy with either TPF (Docetaxel, Cisplatin and 5 Flurouracil) or Cisplatin + 5FU Measurable disease Adequate organ function as evidenced by the following peripheral blood counts and serum biochemistry at enrolment: o Neutrophils ≥1.5 x 109/L o Haemoglobin ≥10 g/dL o Platelets ≥100 x 109/L o Total bilirubin <1.5 upper limit of normal (ULN) o Alanine aminotransferase/serum glutamate pyruvate transaminase(ALT/SGPT) ≤1.5 x ULN Serum creatinine ≤1.5 x ULN. If creatinine is 1.0-1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with a creatinine clearance <60 ml/min should be excluded.
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E.4 | Principal exclusion criteria |
Pure verrucous carcinoma of the penis Squamous cell carcinoma of the penis T1 N1 M0 disease T2 N1 M0 disease Unfit for this regimen as assessed at MDT Contraindication to chemotherapy ECOG > 2 Active peripheral neuropathy grade ≥ 2 Active secondary cancers Other concurrent serious illness or medical condition Inadequate organ function ECG evidence of uncontrolled cardiac arrythmias, angina pectoris and/or hypertension, history of congestive heart failure or myocardial infarctoin within the last 6 months Uncontrolled diabetes mellitus History of severe hypersensitivity reaction(≥ grade 3)to Docetaxel History of severe hypersensitivity reaction (≥ grade 3)to polysorbate 80 containing drugs Active infection requiring systemic antibiotic or anti-fungal medication Particpation in another clinical trial with an investigational drug within 30 days prior to study registration 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 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the activity of Cabazitaxel chemotherapy as assessed by objective response rate |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Response will be evaluated according to radiological response as per RECIST 1.1. The objective response rate for this study is defined as the proportion of patients having achieved partial or complete remission according to their radiological stage at end of cycle 6 compared with radiological stage at diagnosis. Analysis will include tabulation of baseline characteristics of recruited patients. Intention to treat analysis will be used. Baseline characteristics for those patients not completing trial treatment will be tabulated for comparison with treated patients, to ensure the ability to generalise results. Baseline characteristics will include (but are not limited to) demographic data, tumour stage and grade.
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E.5.2 | Secondary end point(s) |
Safety and tolerability Progression free survival Overall survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression free survival will be calculated from the date of study entry until a progression occurs. Progression events are defined as clinical, pathologic or radiological documented disease progression, or death from any cause, Patients free from a progression event will be censored on the date of last follow up. A progression-free survival curve will be generated using the methods of Kaplan and Meier. All patients registered in the study will be included. Median PFS rate will be reported with 95% CIs. Duration of response as measured by Kaplan-Meier at each follow-up, or until progression, will be reported. |
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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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 | Yes |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 31 |