BEVABEL - GETUG-AFU 24
Étude de phase II, non randomisée, d’évaluation de la gemcitabine associée à un sel de platine en combinaison avec le bévacizumab (Avastin®) dans le traitement des carcinomes métastatiques des tubes collecteurs du rein

Phase : II

Type d'essai : Interventionnel

Etat de l'essai : Ouvert

Objectif principal

Evaluer l’efficacité et la tolérance de la gemcitabine associée à un sel de platine en combinaison avec le bévacizumab (Avastin®), chez des patients ayant un cancer métastatique du rein de type carcinome du canal collecteur (tumeur de Bellini) ou cancer médullaire.

Objectifs secondaires

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).

Résumé / Schéma de l'étude

Le patient revra 6 cycles maximum :
J1 et J8: GEMCITABINE 1250 mg/m².
J1 CISPLATIN: 70mg/m² or CARBOPLATIN AUC 5.
J1 BEVACIZUMAB: 15 mg/Kg.

Schéma essai BEVABEL

Critères d'inclusion

  1. Patients should be aged ≥ 18 years at the inclusion.
  2. Patients with histologically confirmed metastatic collecting duct carcinoma (medullary accepted).
  3. Available tumor samples for centralized reading by anatomopathologist.
  4. Patients with or without nephrectomy.
  5. At least one measurable lesion as per RECIST criteria (RECIST v1.1).
  6. Patients naive for anti-angiogenic drugs ; Prior adjuvant chemotherapy of localised disease admitted if it is stopped for more than 12 months at the inclusion date.
  7. No irradiation within 4 weeks before inclusion.
  8. Absolute neutrophil counts (ANC) ≥ 1.5 x 109/L.
  9. Platelets ≥ 100 x 109/L.
  10. Hemoglobin ≥ 9 g/dL.
  11. Hepatic function : AST and ALT  1.5 x ULN (≤ 5 x ULN in case of liver metastases); total bilirubin ≤ 1.5 x ULN (except in case of liver metastases and ≤ 3 x ULN in case of Gilbert's syndrome); alkaline phosphatase < 2 x ULN (≤ 4 x ULN in case of bone metastases).
  12. Renal function : creatinine clearance ≤ 60 mL/min (MDRD calculation method) when using cis-platin and > 30mL/min when using carboplatin.
  13. Absence of proteinuria at baseline defined by < 0.3 g/L of protein on urine sample or < 0.5 g/24h00 on urine collection.
  14. Prothrombin time (TP) or partial thromboplastin time (PTT) strictly less than 50% deviation from normal limits, of international normalized ratio (INR) strictly 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 enrolment. Prophylactic use of anticoagulants is allowed.
  15. ECG with normal or clinically insignificant as per investigator’s judgement sinus rhythm.
  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 6 months after the last study treatment intake.
  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.

Critères de non-inclusion

  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 spinal cord compression or leptomeningeal disease. Please note that patients with asymptomatic brain metastases are eligible.
  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 strictly 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 or 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 gastro-duodenal ulcer.
  13. Patients with untreated bone fracture.
  14. Peripheral neuropathy grade > 2 (Toxicity Criteria-(CTCAE) v4.0.
  15. 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.

Calendrier prévisionnel

Lancement de l'étude : Décembre 2014
Fin estimée des inclusions : Juillet 2019
Nombre de patients à inclure : 41

Etablissement(s) participant(s)

> Centre Antoine Lacassagne (CAL)

(06) Alpes-Maritimes

Dr. Delphine BORCHIELLINI
Investigateur principal

> Institut Paoli-Calmettes (IPC)

(13) Bouches-du-Rhône

Dr. Gwenaëlle GRAVIS MESCAM
Investigateur principal

Coordonnateur(s)

Dr. Nicolas PECUCHET

Hôpital Européen Georges Pompidou - AP-HP

Téléphone : 01 56 09 30 27

Email : nicolas.pecuchet@egp.aphp.fr

Dr. Marc-Olivier TIMSIT

Hôpital Européen Georges Pompidou - AP-HP

Téléphone : 01 56 09 56 45

Email : marc-olivier.timsit@egp.aphp.fr

Promoteur(s)

UNICANCER

Mme Muriel HABIBIAN

Chef de Projet

Téléphone : 01 76 64 78 07

Email : m-habibian@unicancer.fr

Dernière mise à jour le 07 août 2018