Etude : INFINITE / rAd-IFN-MM-301



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
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : INFINITE

Nom : rAd-IFN-MM-301

Traitement : Métastasique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 12/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Phase 3, Open-Label, Randomized, Parallel Group Study to Evaluate the Efficacy and Safety of Intrapleural Administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in Combination With Celecoxib and Gemcitabine in Patients With Malignant Pleural Mesothelioma

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C38 - Tumeur maligne du coeur, du médiastin et de la plèvre
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : STUDY DRUGS: Nadofaragene firadenovec (Recombinant adenovirus vector containing the human interferon alpha-2b gene: rAd-IFN), celecoxib, and gemcitabine

INDICATION: Malignant pleural mesothelioma (MPM)

SITES: Approximately 80 sites globally


OBJECTIVES:

The primary objective of this study is to compare the overall survival (OS) associated with rAd IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen.

The secondary objectives of this study are:

To compare between rAd-IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen, with respect to:
Survival rate at 12 months and every 6 months thereafter;
Progression-free survival (PFS);
Best response (complete response, partial response, or stable disease); and
Safety of rAd-IFN; and
To evaluate rAd-IFN, when administered with celecoxib and gemcitabine, in a sub-set of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen, with respect to viral shedding and biodistribution.

The exploratory objectives of this study are:

• To compare between rAd-IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen, with respect to:

Health-related Quality-of-Life,
The relationship between immunological status and response to treatment, and
Biocorrelates of response to treatment.


POPULATION:
The population for this study is patients with histologically confirmed MPM of epithelioid or biphasic (predominantly [>50%] epithelioid) histology who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen.


STUDY DESIGN AND DURATION:

The study is an open-label, randomized, parallel group study conducted in patients with histologically confirmed MPM of epithelioid or biphasic (predominantly [>50%] epithelioid) histology who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen.

Screening assessments must be completed within 28 days of Study Day 1, and eligible patients will be randomized to either:

Treatment group: rAd-IFN (Study Day 1) + celecoxib (Study Days 1 to 14) + gemcitabine (Study Days 14 and 21 [i.e., Days 1 and 8 of the first gemcitabine treatment cycle], gemcitabine will be repeated every 3 weeks until disease progression/early termination [ET]); or
Control group: celecoxib (Study Days 1 to 14) + gemcitabine (Study Days 14 and 21 [i.e., Days 1 and 8 of the first gemcitabine treatment cycle], gemcitabine will be repeated every 3 weeks until disease progression/ET).

Treatment Phase Patients randomized to receive rAd-IFN (treatment group) will have an intrapleural catheter (IPC) or other intrapleural access device previously in place or inserted for the study, permitting drug administration to an accessible pleural space. The rAd-IFN will be diluted to a volume of 25 mL using sterile normal saline and will be administered directly to the pleural space via the IPC or similar device.

Patients will receive gemcitabine until disease progression/ET. All adverse events will be captured from the time of the main study's informed consent through 30 days after the last dose of study treatment (rAd-IFN, celecoxib, and/or gemcitabine). All treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) will be followed until resolution or stabilization.

Survival Follow-Up Phase Following disease progression, patients will be followed every 3 months for survival. All previously recorded TEAEs and SAEs will be followed until resolution or stabilization.


DOSAGE FORMS AND ROUTE OF ADMINISTRATION:

Patients randomized to the treatment group will receive rAd-IFN (3 × E11 viral particles) on Day 1 of the study, diluted to a total volume of 25 mL using sterile normal saline and administered into the pleural space via an IPC or similar intrapleural device.

All study patients (treatment and control) will receive:
- Celecoxib administered at a dose of 400 mg twice daily orally on Days 1 to 14 of the study; and
- Gemcitabine starting on Study Day 14, using the following treatment regimen: 1250 mg/m2 administered intravenously on Days 1 and 8 of a 21-day gemcitabine cycle and continued every 3 weeks until disease progression/ET.

Phase : III

Stade : Localisé à Localement avancé

2, 3
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Aged 18 years or older and able to give informed consent;
2. Confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (predominantly [>=50%] epithelioid);
3. Measurable disease, per modified RECIST for pleural mesothelioma;
4. Has failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, which may have been chemotherapeutic and/or immunotherapeutic treatment regimens for MPM which included at least 1 anti-folate and platinum combination regimen;
5. Has a pleural space accessible for pleural catheter insertion. Patients with a previously inserted pleural catheter may enroll, and the pre-existing catheter can be used for vector administration as long as it is functional and has no evidence of local infection;
6. Life expectancy >=12 weeks in the judgement of the Investigator;
7. ECOG status of 1 or 0;
8. Female and male patients:
- Female patients must be either postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile upon entry into the study. Female patients of childbearing potential must have a negative pregnancy test upon entry into this study and agree to use a highly effective method of contraception from Screening until 1 month following administration of gemcitabine;
- Male patients must be either surgically sterile or agree to use a double-barrier contraception method from Screening until 1 month post-gemcitabine administration;
9. Adequate laboratory values at screening

Critères de non-inclusion : 1. Is “treatment-naïve” (i.e., has not received at least 1 anti-folate and platinum combination regimen);
2. Has previously received 3 or more lines of systemic chemotherapeutic or immunotherapeutic treatment;
3. Has previously received treatment with gemcitabine;
4.Has stage IV extrathoracic metastatic disease;
5.Inadequate pulmonary function of clinical significance as per Investigator review;
6.Clinically significant pericardial effusion at Screening;
7.Prior therapy(ies), if applicable, must be completed according to the protocol-specified criteria
8.Patient previously treated with IFNs (e.g., for chronic active hepatitis);
9.Suspected/known hypersensitivity to IFN-α2b;
10. Known hypersensitivity to celecoxib or sulfonamides;
11. Impaired cardiac function or clinically significant cardiac disease;
12. Women who are pregnant or breastfeeding;
13. Uncontrolled intercurrent illness
14. Patients with active, known, or suspected auto-immune disease or a syndrome that requires systemic or immunosuppressive agents (oral prednisolone or equivalent at a dose of <=10 mg per day is permitted);
15. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs;
16. History of ulcer disease or gastrointestinal bleeding;
17. Uncontrolled or poorly controlled hypertension requiring 3 or more anti-hypertensive drugs;
18. Patients receiving lithium;
19. Any significant disease which, in the opinion of the Investigator, would place the patient at increased risk of harm if he/she participated in the study;
20. History of malignancy of other organ system within the past 5 years, except treated basal cell or squamous cell carcinoma of the skin, or early stage prostate cancer (stage T2a or smaller, prostate specific antigen <=10 ng/mL, Gleason score <=6); or
21. Has a congenital or acquired immunodeficiency, including patients with known history of infection with human immunodeficiency virus.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03710876
Promoteur :
Trizell Ltd
Type de sponsor : Industriel
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Arnaud Scherpereel

TEC / ARC / IDE :
Eric Wasielewski
eric.wasielewski@
chru-lille.fr
03.20.44.56.12

Ouverture de l'essai : OUVERT

MAJ : 12/09/2019