| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Malignant Pleural Mesothelioma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10059518 |
| E.1.2 | Term | Pleural mesothelioma malignant |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 received 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. |
|
| E.2.2 | Secondary objectives of the trial |
- To compare the following between treatment arms:
o Survival rate at 12 months and every 6 months thereafter;
o Progression-free survival (PFS);
o Best response (complete response, partial response, or stable disease); and
o Safety of rAd-IFN
- To evaluate viral shedding and biodistribution |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Aged 18 years or older and able to give informed consent;
2. Confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (if biphasic, histology must be predominantly [>=50%] epithelioid);
3. Measurable disease, per modified RECIST 1.1 for pleural mesothelioma;
4. Has received 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 IPC or similar device insertion. Patients with a previously inserted IPC or similar device may enroll, and the pre-existing IPC or similar device 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 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 after the last dose of gemcitabine; Female patients of nonchildbearing potential must be either postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile upon entry into the study;
- Male patients must be either surgically sterile or agree to use a double-barrier contraception method from Screening until 6 months after the last dose of gemcitabine administration;
- Where available and in accordance with local practice, male patients must be advised to seek further advice regarding cryoconservation of sperm prior to gemcitabine treatment due to the possibility of infertility after therapy with gemcitabine;
9. Adequate laboratory values at screening |
|
| E.4 | Principal exclusion criteria |
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; Treatment that is split between presurgical resection and post-surgical resection and is the same regimen will be counted as 1 regimen. Patients meeting this condition should be discussed with the Medical Monitor prior to including the patient in the study;
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; Standard of care CT scans completed within 2 weeks prior to Screening may be used in place of the Screening CT scan on a case by-case basis as agreed with the Medical Monitor;
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 (including any of its excipients);
10. Known hypersensitivity to celecoxib (including any of its excipients) or sulfonamides;
11. Known hypersensitivity to gemcitabine (including any of its excipients);
12. Impaired cardiac function or clinically significant cardiac disease;
13. Women who are pregnant or breastfeeding;
14. Uncontrolled intercurrent illness
15. 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);
16. History of asthma, acute rhinitis, nasal polyps, angioneurotic edema, urticaria, or other allergic-type reactions after taking acetylsalicylic acid
or NSAIDs including COX-2 inhibitors;
17. History of ulcer disease or gastrointestinal bleeding;
18. Uncontrolled or poorly controlled hypertension (i.e., blood pressure >160/100 mmHg) requiring 3 or more anti-hypertensive drugs;
19. Heart rate corrected QT interval using Fridericia's formula >470 ms on resting 12-lead electrocardiogram (ECG);
20. Patients receiving lithium;
21. 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;
22. History of a prior malignancy for which treatment was completed <2 years prior to Screening or for which the patient has continued evidence of disease, or concurrent malignancy that is clinically unstable and requires tumor-directed treatment;
23. Has a congenital or acquired immunodeficiency, including patients with known history of infection with human immunodeficiency virus.
24. Has both serum albumin 2.5 to 3.5 g/dL and total bilirubin >1.5 x ULN;
25. History of clinically significant inflammatory bowel disease requiring systemic (parenteral) immunosuppressive therapy within 5 years prior to Screening; or
26. History of galactose intolerance, Lapp lactase deficiency, or glucosegalactose malabsorption. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Death (from any cause) from randomisation |
|
| E.5.2 | Secondary end point(s) |
1. To evaluate survival rate
2. To evaluate PFS
3. To evaluate best response
4. To evaluate the number of patients with CTCAE Grade 3-4
5. To evaluate post-treatment levels of rAd-IFN-related viral DNA in biological samples |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 12 months, and every 6 months thereafter
2. When modified RECIST 1.1 criteria for disease progression are first met, or death from any cause
3. Best response after randomisation
4. Continuous assessment
5. Samples collected up to 28 days after Study Day 1 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Russian Federation |
| United Kingdom |
| United States |
| France |
| Germany |
| Italy |
| Poland |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study (study completion) is defined as the last visit of
the last patient. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 26 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
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