E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced/Metastatic Urothelial Tract or Bladder Cancer |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
|
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 compare Overall Survival (OS) of patients administered Larotaxel in combination with cisplatin versus gemcitabine in combination with cisplatin for the treatment of locally advanced/metastatic urothelial tract or bladder cancer |
|
E.2.2 | Secondary objectives of the trial |
- To compare Progression Free Survival (PFS), Objective Response Rate (ORR), time to definitive deterioration of PS, Duration of Response (DR), and time to definitive 5% weight loss of larotaxel in combination with cisplatin vs. gemcitabine combined with cisplatin.
- To assess the safety and tolerability of Larotaxel in combination with cisplatin and gemcitabine with cisplatin.
- To assess the pharmacokinetics of Larotaxel and cisplatin in this patient population (in selected centers). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC) with locally advanced (T4b) or metastatic (lymph node or visceral) urothelial tract or bladder cancer.
- ECOG Performance Status 0 or 1.
- No prior palliative chemotherapy. |
|
E.4 | Principal exclusion criteria |
- Age < 18 years old. - Disease localized only to the radiation fields without radiologically confirmed progression of the disease within the radiation fields after completion of prior radiotherapy.
PRIOR THERAPY: - (Neo)Adjuvant chemotherapy if < 6 months between end of (Neo)adjuvant chemotherapy and relapse - Less than 6 weeks elapsed from prior radiotherapy (in case of palliative radiotherapy for pain or bleeding control 6-week interval is not mandatory providing the patient recovered from all toxicities) and less than 3 weeks from surgery to time of randomization. Patients pN+ with no residual disease after surgery are not eligible - Treatment with an investigational agent within 4 weeks (6 weeks for immunotherapy) of study enrollment
BIOLOGICAL CRITERIA: - Bone marrow function as defined by absolute neutrophil count < 1.5 x 10e9/L, platelet < 75 x10e9/L, or hemoglobin < 9.0 g/dL. - Alkaline phosphatase (AP) ≤ 2.5 x UNL associated with AST/ALT > 2.5 x UNL, or AP > 2.5 x UNL and ≤ 5.0 x UNL associated with AST/ALT > 1.5 UNL or AP > 5.0 x UNL - Total Bilirubin > 1.0 x UNL - Creatinine > 1.0 x UNL, except in case of creatinine > 1.0 x UNL and ≤ 1.5 x UNL if actual creatinine clearance ≥ 60 ml/min
PAST or CURRENT HISTORY - History or new evidence of brain metastases or leptomeningeal disease (...) - History of another neoplasm. Patients with prior history of either non-metastatic non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery, small field radiation or chemotherapy ≥ 5 years prior to randomization will be eligible (...) - Prior cisplatin as (neo)adjuvant chemotherapy with cumulative dose> 300 mg/m² - Peripheral neuropathy > grade 1 - History of inflammatory bowel disease, significant bowel obstruction. - History of hypersensitivity to platinum, gemcitabine, taxanes, polysorbate 80, or to compounds with similar chemical structures. - Known human immunodeficiency virus (HIV) infection immunodeficiency-syndrome (AIDS)-related illness. - Any other as active illness such as active uncontrolled infections, uncontrolled cardiac disease or hypertension, uncontrolled diabetes that would preclude safe administration of study therapy at the time of randomization (...)
CONCOMITANT TREATMENT - Concurrent treatment with strong inhibitors of CYP P450 3A4 or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to randomization
- Concurrent treatment with strong inhibitors of cytochrome P450 2C8 (gemfibrozile) or patients planning to receive this treatment. For patients who were receiving treatment with such agent, a one-week washout period is required prior to randomization.
Others Refer to the Protocol.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
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 | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
|
The duration of the study is expected to take approximately 3 years and 1 month, which includes 30 months for patients accrual and 7 months follow-up in order to assess median overall survival for the whole population. The study cut-off date will be the date when the required 511 events (deaths) have been observed. But the end of trial is until disease progression, unacceptable toxicity, consent withdrawn or physician decision. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |