Etude : GCISAVE /

ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.

Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : GCISAVE

Situation thérapeutique : Métastatique ou localement avancé

Traitement :

Cadre réglementaire : RIPH2

Dernière MÀJ : 24/11/2020
CIM10 - Localisation(s)
Informations principales
Titre : Gemcitabine-Cisplatin plus avelumab or Gemcitabine-Cisplatin as first-line treatment of patients with locally advanced or metastatic urothelial bladder carcinoma

Spécialité : Voies urinaires
Localisation : C67 - Tumeur maligne de la vessie
Informations complémentaires
Schéma : The study is a prospective therapeutic randomized non-comparative open-label multicenter phase II study.

The study will assess at the same time efficacy and tolerance of GC + avelumab, and will be based on a two-stage Bryant-Day design, used with two co-primary end points: the objective response rate and the incidence of severe toxicity after six cycles of treatment (stopping rules are given in case of inadequate objective response rate or unacceptable toxicity).
A non-comparative control group treated with GC is added to assess efficacy, safety and immunological capacities.
To avoid selection bias, the trial is randomized with a ratio 2:1, 2 patients in the experimental group (GC+ avelumab) for 1 patient in the control group (GC).
Randomization will be stratified on Karnofsky status (≥ 80 vs. < 80).
At the end of 6 cycles of treatment, according to practice, the treatment will be interrupted and the patient followed for tolerance and immunological status for 12 additional months.

- GC (in both arms) ; G : gemcitabine 1000mg/m² on day 1 and day 8 / 3 weeks ; Cisplatin: C: 70 mg/m² on day 1/ 3 weeks.
- +/- Avelumab : 10mg/kg/3 weeks

Phase : II

Stade : Métastatique

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Signed and dated informed consent;
2. Male or female, age ≥18 years at time of informed consent signature;
3. Histological confirmed locally advanced (any T N2-3) or metastatic urothelial bladder carcinoma, eligible to first-line treatment (previous adjuvant treatment must have been given more than one year before);
4. Evidence of progressive disease in the previous 6 months, documented by chest and/or abdominal CT-scan or MRI;
5. Measurable disease according to RECIST 1.1;
6. Karnofsky index ≥ 70%;
7. Availability of a representative formalin-fixed, paraffinembedded (FFPE) tumour specimen (infiltrative urothelial bladder carcinoma or metastasis) collected within 12 months before Cycle 1 Day 1;
8. At least 3 weeks since the end of prior systemic treatment with resolution of all treatment-related toxicity to grade ≤1 (NCI CTCAE 4.0);
9. Palliative local treatment is allowed if performed ≥ 2 weeks prior study entry for radiotherapy, cimentoplasty or minor surgery, and ≥4 weeks for major surgery;
10. Adequate organ function as defined by the following criteria:
a. Absolute White Blood Cells count (WBC) ≥ 2000 cells/mm3
b. Absolute Neutrophils count (ANC) ≥ 1500 cells/mm3
c. Platelets ≥100 000 cells/mm3
d. Hemoglobin ≥ 9.0 g/dL
e. Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
f. Calculated creatinine clearance ≥ 60 mL/min
11. Women of childbearing potential must have a negative serum βHCG or urine pregnancy test within 7 days prior to initiation of treatment; Both sexually active females and males (and their female partners) patients must agree to use two methods of effective contraception one of them being a barrier method, or to abstain from sexual activity during the study, for at least 3 months after the last administration of study treatment;
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures;
13. Patient affiliated to a social security system or beneficiary of the same.

Critères de non-inclusion : 1. Other prior first-line therapy;
2. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; focal radiation therapy less than 14 days prior to the first day of the first cycle;
3. Other invasive malignancy within 3 years (except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast);
4. Persisting toxicity related to prior therapy (NCI CTCAE v.4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable;
5. Symptomatic central nervous system (CNS) metastases or untreated CNS metastases requiring concurrent treatment;
6. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication;
7. Uncontrolled adrenal insufficiency;
8. Active chronic liver disease;
9. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
10. Active infection requiring systemic antibiotic or anti-fungal medication;
11. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines;
12. Current use of immunosuppressive medication, EXCEPT for the following:
a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);
13. Major surgery less than 28 days prior to the first day of the first cycle. Minor surgery less than 14 days prior to the first day of the first cycle;
14. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible;
15. History of primary immunodeficiency;
16. History of organ transplant including allogeneic stem-cell transplantation;
17. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3);
18. Women who are pregnant or lactating;
19. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
20. Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
Informations relatives au promoteur
Promoteur :
CHU de Bordeaux
Type de sponsor : Institutionnel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN
Apicrypt :

Investigateur :
Florence JOLY


Statut de l'essai : CLOS

MAJ : 24/11/2020