A Phase III, 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
- Conditions
- Malignant Pleural MesotheliomaMedDRA version: 20.0Level: PTClassification code 10059518Term: Pleural mesothelioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003169-82-FR
- Lead Sponsor
- Trizell Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270
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-a2b;
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to compare the overall survival 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.;Secondary Objective: - To compare the following between treatment arms:<br> o Survival rate at 12 months and every 6 months thereafter;<br> o Progression-free survival (PFS);<br> o Best response (complete response, partial response, or stable disease); and<br> o Safety of rAd-IFN<br>- To evaluate viral shedding and biodistribution;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: Death (from any cause) from randomisation
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. To evaluate survival rate<br>2. To evaluate PFS<br>3. To evaluate best response<br>4. To evaluate the number of patients with CTCAE Grade 3-4<br>5. To evaluate post-treatment levels of rAd-IFN-related viral DNA in biological samples ;Timepoint(s) of evaluation of this end point: 1. At 12 months, and every 6 months thereafter<br>2. When modified RECIST criteria for disease progression are first met, or death from any cause<br>3. Best response after randomisation<br>4. Continuous assessment <br>5. Samples collected up to 28 days after Study Day 1