Etude : STRONG / D4191C00068

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 : STRONG / D4191C00068

Situation thérapeutique : Adjuvant / Métastatique ou localement avancé

Traitement :

Cadre réglementaire : RIPH2

Dernière MÀJ : 25/09/2018
CIM10 - Localisation(s)
Informations principales
Titre : An Open-Label, Multi-Centre, Safety Study of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.

Spécialité : Voies urinaires
Localisation : C67 - Tumeur maligne de la vessie
Informations complémentaires
Schéma :
Experimental: Combination therapy

Combination therapy (durvalumab + tremelimumab) : Patients will receive the combination therapy followed by monotherapy via intravenous (IV) infusion once Q4W:
Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) and
Durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.
Biological: MEDI4736 (Durvalumab)
Biological: MEDI4736 (Durvalumab) + Tremelimumab
Experimental: Monotherapy
Monotherapy (Durvalumab 1,500 mg): Patients will receive durvalumab 1,500 mg via IV infusion Q4W on Week 0.
Intervention: Biological: MEDI4736 (Durvalumab)

Phase : IIIb

Stade : Localement avancé à Métastatique

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion :
- Must have a life expectancy of at least 12 weeks.
- Age ≥ 18 years at the time of screening. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Disease not amendable to curative surgery
- Eastern Cooperative Oncology Group (ECOG) performance status as defined in the specific module.
- Body weight >30 kg.
- No prior exposure to anti-programmed death (PD) 1 or anti-PD-ligand (L) 1.
- Adequate organ and marrow function.
- Female patients of childbearing potential (i.e., not surgically sterile or post-menopausal) who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy.

- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy.

-For inclusion in the Module A of the study patients should fulfill the following criteria:

Histologically or cytologicaly confirmed locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract (including the urinary bladder, ureter, urethra and renal pelvis)
Disease that has progressed during or after at least one previous platinum or nonplatinum based chemotherapy, either for metastatic disease or progressive disease less than 12 months after adjuvant or neo-adjuvant chemotherapy
ECOG performance status 0-2

Critères de non-inclusion : - Involvement in the planning and/or conduct of the study.
- Previous IP assignment in the present study.
- Concurrent enrollment in another clinical study or another sub-study of this protocol, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- Participation in another clinical study with an IP and receipt of any investigational anticancer therapy during the last / within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
- Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for cancer treatment.
- Local treatment of isolated lesions for palliative intent is acceptable (e.g., local surgery or radiotherapy).
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
- History of allogenic organ transplantation.
- Uncontrolled intercurrent illness (ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- History of another primary malignancy, leptomeningeal carcinomatosis and active primary immunodeficiency.
- Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on baseline brain imaging (please refer to RECIST for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
- Active infection including tuberculosis, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (positive HIV ½ antibodies).

- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab.

- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).

- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

- Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic composition to the study drug(s), or any of the study drug excipients.
- Any unresolved NCI CTCAE Grade ≥2 toxicities from prior anti-cancer therapy with the exception of vitiligo, alopecia, and the laboratory values defined in the inclusion criteria.

- Pregnant or breastfeeding women or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy.

- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
CHU de Rouen - 1 Rue de Germont - 76000 ROUEN

Investigateur :
Chrsitian PFISTER


Statut de l'essai : OUVERT

MAJ : 25/09/2018