| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic collecting duct carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Metastatic collecting duct carcinoma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
| 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 | 10073252 |
| E.1.2 | Term | Carcinoma of the collecting ducts of Bellini |
| 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 gemcitabine plus platinum salt in combination with bevacizumab using a co-primary endpoint composed of Objective Response Rate (CR or PR according to RECIST criteria) and Progression-Free Survival rate at 6 months. |
|
| E.2.2 | Secondary objectives of the trial |
Evaluation of the Progression-free survival (PFS)
Evaluation of the Overall Survival (OS)
Evaluation of the Safety
To set up several biological material bank resources (plasma sample, tumor and for patients who underwent nephrectomy, non tumor tissu) for further ancillary studies (molecular, immunologic and pharmacogenomic studies) |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| An ancillary study is not yet defined however, for further researches, biological samples will be collected and stored. Biological studies realized using human biological samples (blood, tumor tissues) are necessary to advance the knowledge of diseases and could help in devising newer and more effective treatments. |
|
| E.3 | Principal inclusion criteria |
1-Patients with histologically confirmed metastatic collecting duct carcinoma,
2-Available tumor samples for centralized reading by anatomopathologist,
3-Patients with or without nephrectomy,
4-At least one measurable lesion as per RECIST criteria (RECIST v1.1),
5-No prior chemotherapy nor anti-angiogenic drugs (naive patients),
6- No irradiation within 4 weeks before inclusion,
7-Absolute neutrophil counts (ANC) ≥ 1.5 x 10^9/L,
8- Platelets ≥100 x 10^9/L,
9- Hemoglobin ≥9 g/dL,
10- Hepatic function : AST and ALT ≤ 1.5 x ULN (≤ 4 x ULN in case of liver metastases); total bilirubin ≤ 1.5 x ULN; alkaline phosphatase < 2 x ULN (≤ 4 x ULN in case of bone metastases),
11- Renal function : creatinine clearance ≥ 60 mL/min (MDRD calculation method),
12- Absence of proteinuria at baseline defined by < 0.3 g of protein on urine sample or < 0.5g/24h00 on urine collection,
13- Prothrombin time (TP) or partial thromboplastin time (PTT) less than 50% deviation from normal limits, of international normalized ratio (INR) below 2,
Note: The use of full-dose oral or parenteral anticoagulants as well as aspirin or clopidogrel is permitted as long as the INR or a PTT is within therapeutic limits (according to the medical standard of the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of study enrollment. Prophylactic use of anticoagulants is allowed.
14- ECG with normal sinus rhythm and no clinically significant changes,
15- Patients should be aged ≥ 18 years at the inclusion,
16- ECOG Performance Status: 0 – 2,
17- Estimated life expectancy ≥ 12 weeks,
18- Patients who have received the information sheet, dated and signed the informed consent form,
19- Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for 4 months after the last study treatment intake for women and 6 months for men.
20- Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory
tests and other study procedures,
21- Patients affiliated to the Social Security System, |
|
| E.4 | Principal exclusion criteria |
1. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment,
2. Prior systemic treatment with chemotherapy or anti-angiogenic tyrosine kinase inhibitors such as axitinib, sunitinib, sorafenib, pazopanib, tivozanib, mTOR inhibitor (Temsirolimus or everolimus) and targeted VEGF drugs such as bevacizumab and VEGF trap,
3. Evidence of current central nervous system (CNS) metastases or spinal cord compression. If CNS metastases are suspected, patient should undergo an MRI or CT-Scan of the brain (with contrast, if possible) within 28 days prior to inclusion,
4. Another histological type of renal cancer
5. Other malignancy within 3 years prior to inclusion (except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix, and/or pT1/a bladder cancer),
6. Uncontrolled hypertension (≥160 mm Hg systolic and/or ≥ 90 mm Hg diastolic) while receiving medication,
7. Cardio-vascular disorders: congestive heart failure ≥ NYHA II, myocardial infarction or coronary artery bypass graft in the previous six months, ongoing severe or unstable angina,
8. LVEF value less than 50%,
9. Current or recent (within 2 weeks of study enrolment) initiation of aspirin, clopidogrel), oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes.
10. History of clinically significant hemorrhagic of thromboembolic events in the past six months, or known inherited predisposition to bleeding or thrombosis or History of abdominal fistula, GI
perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment; History of haemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month of study enrolment,
11. Patients who underwent, according to the investigator, a significant surgery such as but not limited to , abdominal, thoracic or neurologic surgery within 28 days before the first treatment
administration or patient with a wound that is not already healed at the first treatment administration or patients who underwent a minor surgical procedure including placement of a vascular access device, within 2 days of the first study treatment,
12. Patients with active ulcer,
13. Patients with untreated bone fracture,
14. Peripheral neuropathy grade ≥ 2 (Toxicity Criteria-(CTCAE) v4.0),
15. Including patients with active infection requiring intravenous antibiotics at the time of first study treatment,
16. In the opinion of the investigator, any evidence of other severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease), or any other acute or chronic medical condition that would make the patient inappropriate with this study,
17. Immunocompromised patients, including known seropositivity for human immunodeficiency virus (HIV),
18. Known hypersensitivity to any component of the investigational drugs or excipients,
19. Pregnant or lactating women,
20. Person deprived of their liberty or under judicial protection (including guardianship),
21. Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering
compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial. Those conditions should be discussed with the patient before registration in the trial, |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is composed of:
- the objective response rate (CR or PR) according to RECIST criteria (V1.1)
- the progression-free survival (PFS) rate at 6 months , PFS is defined as absence of disease progression or death |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Progression-free survival (PFS) will be calculated from the date of the first dose of trearment to the date of progression or death (whichever comes first), or last date with no progression;
- The Overall Survival (OS) will be calculated from the date of the first dose of trearment to the date of death (whatever the cause) or the date of last follow-up;
- The toxicity will be evaluated according to the NCI-CTC version 4.0; |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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) | 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 | 13 |
| 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
|
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 6 |
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