E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cisplatin-resistant germ cell cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with metastatic germ cell cancer and relapse after two or more courses of cisplatin-based chemotherapy or after high-dose chemotherapy. |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10043321 |
E.1.2 | Term | Testicular germ cell cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
To evaluate the efficacy of cabazitaxel as monotherapy for the treatment of germ cell cancer. Efficacy is defined objective responses according to RECIST 1.1 |
|
E.2.2 | Secondary objectives of the trial |
Disease control rate (SD + PR + CR)
Progression-free survival
Overall survival
Safety profile
Change of serum tumor markers |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Male patients ≥ 18 years old
· Histologically verified metastatic GCC (germ cell cancer of the testicle or extragonadal GCC originating from retroperitoneum or mediastinum)
· Disease progression during cisplatin-based chemotherapy or Disease progression or relapse after high-dose chemotherapy or Disease progression or relapse after at least 2 different platin-based
· ECOG Performance Status (PS): 0-2
· Life expectancy ≥3 months
· Adequate function of liver, kidneys and bone marrow at baseline
· Signed written informed consent |
|
E.4 | Principal exclusion criteria |
· Systemic antitumor treatment within 21 days before study entry
· Simultaneous radiotherapy to the only target lesion
· Patients unwilling or unable to comply with the protocol
· Patients with unstable angina pectoris, myocardial infarction ≤ 6 months prior to first study treatment, congestive heart failure NYHA III-IV or serious uncontrolled cardiac arrhythmias
· Patients with an active or uncontrolled infection
· Patients who have a history of another primary malignancy and are off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer
· Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g. intra-thoracic, intra-abdominal, or intra-pelvic) or significant traumatic injury, or who have not recovered from the side effects of any of the above within 6 weeks
· Patients who have participated in another interventional clinical trial within 30 days before study entry
· Other serious medical conditions that could impair the ability of the patient to participate in the study
· Active infection requiring systemic antibiotic-, anti-viral-, or antifungal medication
· Neuropathy ≥ Grade 2
· Patient with reproductive potential not implementing accepted and effective method of contraception during the whole study period and up to 6 months after the last dose of cabazitaxel.
· One or more of the following cabazitaxel-specific requirements:
- History of severe hypersensitivity reaction (≥ Grade 3) to docetaxel
- History of severe hypersensitivity reaction (≥ Grade 3) to polysorbate 80 containing drugs
- Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5
- Concurrent or planned treatment with OATP1B1 substrates within 12 hours before- or 3 hours after application of cabazitaxel |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) by radiologic response according to RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor measurements by a CT scan or MRI will be performed at screening within 2 weeks prior to the first dose of study drug. During the study period, the CT scan/MRI will be performed every 9 weeks (± one week), and at the time of discontinuation of study drug (within 2 weeks). The same type of scan (CT or MRI) used at screening must be used for all subsequent follow-up assessments. A partial or a complete response warrants a confirmation no sooner than 4 weeks after its observation. |
|
E.5.2 | Secondary end point(s) |
· Safety profile /Adverse events (AE)
· Disease control rate (SD + PR + CR)
· Progression-free survival (PFS) -time from inclusion to the date of disease progression
· Overall survival (OS) - time from inclusion to the date of death from any cause
· Change of serum tumormarkers (AFP, beta-betaHCG, LDH)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumor measurements by a CT scan or MRI will be performed at screening within 2 weeks prior to the first dose of study drug. During the study period, the CT scan/MRI will be performed every 9 weeks (± one week), and at the time of discontinuation of study drug (within 2 weeks). The same type of scan (CT or MRI) used at screening must be used for all subsequent follow-up assessments. A partial or a complete response warrants a confirmation no sooner than 4 weeks after its observation.
Tumor markers (AFP, betaHCG) will be assessed every 3 weeks.
|
|
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.8.3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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
|
Definition of the end of the trial is Last Patient Last Visit |
|
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 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |