Malignant pleural mesotheliona pleural cancer
Conditions
Interventions
STUDY DRUGS: Nadofaragene firadenovec (Recombinant adenovirus vector containing
the human interferon alpha-2b gene: rAd-IFN), celecoxib, and gemcitabine
Sponsors
Trizell Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 (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
Exclusion criteria
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; 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-*2b; 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is OS, defined as time to death (from any cause) from randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy endpoints are: * To evaluate survival rate at 12 months, defined as the number of deaths (from any cause) at 12 months from randomization, and every 6 months thereafter; * To evaluate PFS, defined as the time from randomization to the time when the modified Response Evaluation Criteria in Solid Tumor criteria for disease progression are first met, or when death from any cause occurs; and * To evaluate best response, defined as the best response after randomization (complete response, partial response, or stable disease). The secondary safety endpoints are: * To evaluate the number of patients with Common Terminology Criteria for Adverse Events Grade 3 or 4; and * To evaluate post-treatment levels of rAd-IFN-related viral DNA in biological samples collected up to 28 days after Study Day 1 in a sub-set of patients. The exploratory efficacy endpoints are: * Change in total score and individual components of the EQ-5D-5L and Lung Cancer Symptom Scale-mesothelioma from baseline (randomization) to each successive cycle of gemcitabine, * Correlation between the presence of adenovirus type 5 neutralizing antibodies prior to treatment and survival (death from any cause), * Correlation between pre- and post-treatment levels of serum mesothelin and treatment outcomes, and * Correlation between pre- and post-treatment levels of serum fibulin-3 and treatment outcomes. | — |
Countries
Netherlands
Outcome results
None listed