Malignant Pleural MesotheliomaPhase 3INFINITENCT03710876
Efficacy & Safety of rAd-IFN Administered With Celecoxib & Gemcitabine in Patients With Malignant Pleural Mesothelioma
A Phase 3 study testing rAd-IFN, Celecoxib Oral Product and Gemcitabine in people with Malignant Pleural Mesothelioma, run by Ferring Ventures Limited at 29 sites in 9 countries.
Trial summary
This study will evaluate intrapleural administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in combination with Celecoxib and Gemcitabine in patients with histologically confirmed Malignant Pleural Mesothelioma (MPM) who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- rAd-IFN, Celecoxib Oral Product and Gemcitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 29 sitesin 9 countries
- Study dates
- 21 Jan 2019to 16 Jan 2026
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who meet all of the following criteria will be eligible to participate in the study:
- Aged 18 years or older at the time of consent;
- Able to give informed consent;
- Has a confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (if biphasic, histology must be predominantly [50%] epithelioid). Histological diagnosis of MPM will be confirmed centrally using specimens or slides from tumor specimens obtained at the time of initial presentation or a subsequent procedure. Central confirmation of diagnosis with immunohistochemistry will be performed, and independent central confirmation will be required for study entry;
- Measurable disease, per modified Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 (see Section 7) for pleural mesothelioma;
- 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;
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- Adjuvant or neoadjuvant therapy represent 1 line of therapy each;
- Patients who have undergone primary surgical resection and/or radiation therapy to the pulmonary site are eligible to participate. For clarity, surgical resection and/or radiation therapy to the pulmonary site are not exclusionary and are not considered a line of therapy;
- Treatment that is split between pre-surgical 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;
- Has a pleural space accessible for IPC or similar device insertion. Patients with a previously inserted IPC or similar device may be enrolled, 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;
- Life expectancy 12 weeks in the judgement of the Investigator;
- Eastern Cooperative Oncology Group (ECOG) status of 1 or 0;
- 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;
- Highly effective methods of contraception that result in a low failure rate (i.e., <1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence;
- True abstinence, when in line with the preferred and usual lifestyle of the patient, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 1 month after the last dose of gemcitabine. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception; and
- Female patients of non-childbearing 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; o 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; and
- Adequate laboratory values at Screening:
- Hemoglobin 9 g/dL;
- White blood cell count 3500/µL;
- Absolute neutrophil count 1500/µL;
- • Platelet count 100,000/µL;
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) below the upper limit of normal (ULN). It is expected that patients receiving anticoagulation therapy will not have INR and aPTT results that fall within normal limits. It is not intended to exclude these patients and, therefore, medical discretion is permitted for patients who have clinically acceptable results in regards to their current concomitant anticoagulant therapy;
- Aspartate aminotransferase (AST) 3 × ULN;
- Alanine aminotransferase (ALT) 3 × ULN;
- Total bilirubin 2 × ULN;
- Estimated glomerular filtration rate (calculated using the Modification of Diet in Renal Disease study equation [see Appendix B]) 50 mL/min/1.73 m2; and
- Serum albumin 2.5 g/dL.
Who cannot join
- Patients who meet any of the following criteria will be excluded from participation in the study:
- Is "treatment-naïve" (i.e., has not received at least 1 anti-folate and platinum combination regimen);
- Has previously received 3 or more lines of systemic chemotherapeutic or immunotherapeutic treatment. Treatment that is split between pre-surgical 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;
- Has previously received treatment with gemcitabine;
- Has stage IV extrathoracic metastatic disease;
- Inadequate pulmonary function of clinical significance as per Investigator review;
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- Clinically significant pericardial effusion (i.e., as judged by the Investigator and/or requiring drainage) detected by computed tomography (CT) scan 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;
- Prior therapy(ies), if applicable, must be completed according to the criteria below prior to vector administration:
- Cytotoxic chemotherapy, at least 21 days from last dose;
- Non-cytotoxic chemotherapy (e.g., small molecule inhibitor), at least 14 days from last dose;
- Monoclonal antibody, at least 30 days from last dose;
- Non-antibody immunotherapy (e.g., tumor vaccine), at least 42 days from last dose;
- Radiotherapy, at least 14 days from last local site radiotherapy;
- Hematopoietic growth factor, at least 14 days from last dose; or
- Study drug, 30 days or 5 half-lives, whichever is longer, from last dose;
- Patient previously treated with IFNs (e.g., for chronic active hepatitis);
- Suspected/known hypersensitivity to IFN-α2b or rAd-IFN (including any of its excipients);
- Known hypersensitivity to celecoxib (including any of its excipients) or sulfonamides;
- Known hypersensitivity to gemcitabine (including any of its excipients);
- Impaired cardiac function or clinically significant cardiac disease including the following:
- New York Heart Association class III or IV congestive heart failure;
- Myocardial infarction within the last 12 months; and
- Patients known to have impaired left ventricular ejection fraction per institutional standards and of clinical significance as per Investigator review;
- Women who are pregnant or breastfeeding;
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, depression, or psychiatric illness/social situations within the last 12 months;
- 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); NOTE: patients with vitiligo, residual hypothyroidism due to auto immune disease only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll;
- 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;
- History of ulcer disease or gastrointestinal bleeding;
- Uncontrolled or poorly controlled hypertension (i.e., blood pressure >160/100 mmHg) requiring 3 or more anti-hypertensive drugs;
- Heart rate corrected QT interval using Fridericia's formula >470 ms on resting 12-lead electrocardiogram (ECG);
- Patients receiving lithium;
- 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;
- 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;
- Has a congenital or acquired immunodeficiency, including patients with known history of infection with human immunodeficiency virus;
- Has both serum albumin 2.5 to 3.5 g/dL and total bilirubin >1.5 ULN;
- History of clinically significant inflammatory bowel disease requiring systemic (parenteral) immunosuppressive therapy within 5 years prior to Screening; or
- History of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
Trial locations and contacts
29 sites in 9 countries.
29 sites in 9 countries
United States7 sites
Marlene & Stewart Greenbaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
University of Maryland Medical Center
Baltimore, Maryland, 21201
University of California, Los Angeles (UCLA) - Medical Center
Los Angeles, California, 90059
Masonic Cancer Center - University of Minnesota
Minneapolis, Minnesota, 55455
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of California, San Francisco (UCSF)
San Francisco, California, 94158
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
France7 sites
Institut Bergonie
Bordeaux, 33076
CHRU de Brest - Hopital Augustin Morvan
Brest, 29200
CHU de Caen - Hopital Cote de Nacre
Caen, 14033
CHRU de Lille
Lille, 59037
Institut Curie - Oncologie Medicale
Paris, 75248
Centre Hospitalier Lyon Sud
Pierre-Bénite
CHU de Nantes - Hôpital Nord Laennec
Saint-Herblain, 44093
United Kingdom5 sites
Beatson, West of Scotland Cancer Centre
Glasgow, Scotland, G12 0YN
Guy's and St. Thomas' NHS Trust
London, SE1 9RT
Churchill Hospital
Oxford, Oxford, OX3 7LJ
Derriford Hospital ; Derriford Hospital
Plymouth, Devon, PL6 8DH
Royal Marsden Foundation Trust
Sutton, Surrey, SM2 5PT
Australia2 sites
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Monash Medical Centre
Clayton, Victoria, 3168
Germany2 sites
Evangelisches Krankenhaus Hamm
Hamm, 59063
Universitatsklinikum Regensburg
Regensburg, 93053
Poland2 sites
Med Polonia Sp. z o.o.
Poznan, 60-693
Centrum Onkologii Instytut im. Marii Sklodowskiej - Curie, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow
Warsaw, ul. Roentgena 5
Russia2 sites
Petrov National Medical Research Center of Oncology
Saint Petersburg, 197758
Volgograd Regional Clinical Oncology Dispensary
Volgograd, 404130
Canada1 site
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
Québec, Sainte-Foy, G1V 4G5
Italy1 site
Azienda Ospedaliero Universitaria Senese, Cancer Immunotherapy
Siena, Tuscany, 53100
About this study
Official title: A 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
This study will evaluate intrapleural administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in combination with Celecoxib and Gemcitabine in patients with histologically confirmed Malignant Pleural Mesothelioma (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.
Eligible patients will be randomized 1:1 to either:
Read more
- Treatment group: rAd-IFN + Celecoxib followed by Gemcitabine
- Control group: Celecoxib followed by Gemcitabine
Patients randomized to the treatment group will receive rAd-IFN administered into the pleural space via an Intrapleural catheter (IPC) or similar intrapleural device on study Day 1.
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
Read the detailed description
TITLE: A 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
PROTOCOL NUMBER: rAd-IFN-MM-301
STUDY DRUGS: Nadofaragene firadenovec (Recombinant adenovirus vector containing the human interferon alpha-2b gene: rAd-IFN), celecoxib, and gemcitabine
PHASE: 3
INDICATION: Malignant pleural mesothelioma (MPM)
SPONSOR: Ferring Ventures Ltd.
SITES: Up to 45 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 MPM and confirmed epithelioid or biphasic histology (if biphasic, histology must be predominantly [>50%] epithelioid) 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.
Screening assessments must be completed within 28 days prior to 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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and 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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and 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 similar device either 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.
The IPC or similar device will then be flushed with up to 20 mL of sterile normal saline.
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.
Clinical Follow-Up Phase Following disease progression/ET, patients in the rAd-IFN treatment group will be followed every 6 months (±14 days) for survival and safety for up to 5 years after receiving the first dose of rAd-IFN, assuming consent has not been withdrawn. All previously recorded TEAEs and SAEs will be followed until resolution or stabilization. Patients in the control group will not continue in the clinical Follow-up phase and study participation will conclude after end of study treatment.
DOSAGE FORMS AND ROUTE OF ADMINISTRATION:
Patients randomized to the treatment group will receive rAd-IFN (3 × 1011 viral particles) on Study Day 1, diluted to a total volume of 25 mL using sterile normal saline and administered into the pleural space via an IPC or similar device. The IPC or similar device will then be flushed with up to 20 mL of sterile normal saline.
All study patients (treatment and control) will receive:
- Celecoxib administered at a dose of 400 mg twice daily orally on Study Days 1 to 14; 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, unless the cycle is modified due to toxicity/delay, and continued every 3 weeks until disease progression/ET.
STATISTICAL ANALYSES:
The primary analysis of the primary endpoint is a comparison of the OS curves between the 2 treatment groups using a log-rank test. A Cox proportional hazards model with treatment as an explanatory variable will be used to assess the magnitude of the treatment difference in OS. The hazard ratio and the associated 95% confidence interval obtained from the Cox proportional hazards model will be presented.
The median OS and the 95% confidence interval for each treatment group will be estimated using the Kaplan-Meier method and summarized by treatment group. Plots of the Kaplan-Meier curve of OS will be presented by treatment group.
Secondary analyses of the primary endpoint will include a comparison of the survival rates at various time points since randomization.
Secondary time-to-event endpoints will be analysed in the same manner as the primary efficacy endpoint.
Categorical efficacy endpoints will be summarized and compared between groups using Fisher's exact test.
The nature, incidence, severity, relatedness, expectedness, seriousness, and outcome of TEAEs will be summarized by treatment group for safety analyses.
SAMPLE SIZE DETERMINATION:
The planned sample size is approximately 50 patients. The sample size is not based on statistical considerations. Patient recruitment into the study has been significantly slower than expected due to several technical study challenges. Therefore, Trizell has decided to discontinue screening and enrolment into the study after a total of approximately 50 patients have been randomized to treatment. It is anticipated that approximately 44 events (equivalent to 89% of the planned 50 enrolled patients) will be observed 24 months after the last patient is randomized. The final analysis of the study will be conducted after the forty-fourth event (death) or 30 months after the last patient is randomized, whichever occurs first.
DATA AND SAFETY MONITORING BOARD:
An independent Data and Safety Monitoring Board (DSMB) will be convened for this study to monitor safety, efficacy, and study integrity. All aspects of the DSMB's scope of review and procedures will be detailed in a DSMB charter.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- rAd-IFN, Celecoxib Oral Product, Gemcitabine
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAd-IFNBiological
Also called Nadofaragene firadenovec
Adenovirus-Delivered Interferon Alpha-2b
Celecoxib Oral ProductDrug
Also called COX II Inhibitor
400 mg twice daily
GemcitabineDrug
Also called Chemotherapy
1250 mg/m2 administered intravenously on Days 1 and 8 of a 21-day cycle and continued every 3 weeks until disease progression/ early termination
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Active comparator | 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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and repeated every 3 weeks until disease progression/early termination [ET] Receives: Biological: rAd-IFN; Drug: Celecoxib Oral Product; Drug: Gemcitabine |
| Control Group | Placebo comparator | 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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and repeated every 3 weeks until disease progression/ET. Receives: Drug: Celecoxib Oral Product; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Time to death (from any cause) from randomization
Measured: 4 years and 8 months
Secondary outcomes (4)
Progression Free Survival
Time measured in months, from randomization to the time when the modified Response Evaluation Criteria in Solid Tumour criteria for disease progression are first met, or when death from any cause occurs
Measured: 4 years and 8 months
Best Response: Objective Response Rate (ORR)
Best overall response (BOR) was defined as the best response designation, in the order of Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE), for each patient that was recorded between the date of randomization and the date of documented disease progression per mRECIST or mRECIST version 1.1, or the date of subsequent anticancer therapy or cancer-related surgery (i.e., surgical resection of tumour), whichever occurred first. ORR was defined as the proportion of patients with a BOR of CR or PR.
Measured: 4 years and 8 months
Best Response: Disease Control Rate (DCR)
Disease control rate (DCR) was defined as the proportion of patients with a BOR of CR, PR, or Stable Disease (SD).
Measured: 4 years and 8 months
Best Response: Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) was defined as the proportion of patients with a BOR of CR, PR, or SD >/= 6 months.
Measured: 4 years and 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2018
- Study start21 Jan 2019
- Primary completion29 Mar 2024
- Study completion16 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferring Ventures Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Pennsylvania
- Responsible party
- Sponsor
- Investigators
- Daniel Sterman, MD, Principal investigator, NYU Langone Laura and Isaac Perlmutter Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03710876
- Sponsor's protocol ID
- rAd-IFN-MM-301
- Other IDs
- 2017-003169-82, 2017
- Acronym
- INFINITE
- Status last verified
- Apr 2026
- First submitted
- 22 Jun 2018
- Last updated
- 21 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 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
- ClinicalTrials.gov ID
- NCT03710876
- Acronym / sponsor ID
- INFINITE / rAd-IFN-MM-301
- Conditions
- Malignant Pleural Mesothelioma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Ferring Ventures LimitedIndustry (pharma, biotech, devices)
- Collaborators
- University of Pennsylvania
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 29 Mar 2024 (actual)
- Study completion
- 16 Jan 2026 (actual)
- First posted
- 18 Oct 2018 (actual)
- Results
- Posted 20 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate intrapleural administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in combination with Celecoxib and Gemcitabine in patients with histologically confirmed Malignant Pleural Mesothelioma (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.
Eligible patients will be randomized 1:1 to either:
- Treatment group: rAd-IFN + Celecoxib followed by Gemcitabine
- Control group: Celecoxib followed by Gemcitabine
Patients randomized to the treatment group will receive rAd-IFN administered into the pleural space via an Intrapleural catheter (IPC) or similar intrapleural device on study Day 1.
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
Detailed description
TITLE: A 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
PROTOCOL NUMBER: rAd-IFN-MM-301
STUDY DRUGS: Nadofaragene firadenovec (Recombinant adenovirus vector containing the human interferon alpha-2b gene: rAd-IFN), celecoxib, and gemcitabine
PHASE: 3
INDICATION: Malignant pleural mesothelioma (MPM)
SPONSOR: Ferring Ventures Ltd.
SITES: Up to 45 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 MPM and confirmed epithelioid or biphasic histology (if biphasic, histology must be predominantly [>50%] epithelioid) 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.
Screening assessments must be completed within 28 days prior to 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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and 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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and 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 similar device either 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.
The IPC or similar device will then be flushed with up to 20 mL of sterile normal saline.
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.
Clinical Follow-Up Phase Following disease progression/ET, patients in the rAd-IFN treatment group will be followed every 6 months (±14 days) for survival and safety for up to 5 years after receiving the first dose of rAd-IFN, assuming consent has not been withdrawn. All previously recorded TEAEs and SAEs will be followed until resolution or stabilization. Patients in the control group will not continue in the clinical Follow-up phase and study participation will conclude after end of study treatment.
DOSAGE FORMS AND ROUTE OF ADMINISTRATION:
Patients randomized to the treatment group will receive rAd-IFN (3 × 1011 viral particles) on Study Day 1, diluted to a total volume of 25 mL using sterile normal saline and administered into the pleural space via an IPC or similar device. The IPC or similar device will then be flushed with up to 20 mL of sterile normal saline.
All study patients (treatment and control) will receive:
- Celecoxib administered at a dose of 400 mg twice daily orally on Study Days 1 to 14; 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, unless the cycle is modified due to toxicity/delay, and continued every 3 weeks until disease progression/ET.
STATISTICAL ANALYSES:
The primary analysis of the primary endpoint is a comparison of the OS curves between the 2 treatment groups using a log-rank test. A Cox proportional hazards model with treatment as an explanatory variable will be used to assess the magnitude of the treatment difference in OS. The hazard ratio and the associated 95% confidence interval obtained from the Cox proportional hazards model will be presented.
The median OS and the 95% confidence interval for each treatment group will be estimated using the Kaplan-Meier method and summarized by treatment group. Plots of the Kaplan-Meier curve of OS will be presented by treatment group.
Secondary analyses of the primary endpoint will include a comparison of the survival rates at various time points since randomization.
Secondary time-to-event endpoints will be analysed in the same manner as the primary efficacy endpoint.
Categorical efficacy endpoints will be summarized and compared between groups using Fisher's exact test.
The nature, incidence, severity, relatedness, expectedness, seriousness, and outcome of TEAEs will be summarized by treatment group for safety analyses.
SAMPLE SIZE DETERMINATION:
The planned sample size is approximately 50 patients. The sample size is not based on statistical considerations. Patient recruitment into the study has been significantly slower than expected due to several technical study challenges. Therefore, Trizell has decided to discontinue screening and enrolment into the study after a total of approximately 50 patients have been randomized to treatment. It is anticipated that approximately 44 events (equivalent to 89% of the planned 50 enrolled patients) will be observed 24 months after the last patient is randomized. The final analysis of the study will be conducted after the forty-fourth event (death) or 30 months after the last patient is randomized, whichever occurs first.
DATA AND SAFETY MONITORING BOARD:
An independent Data and Safety Monitoring Board (DSMB) will be convened for this study to monitor safety, efficacy, and study integrity. All aspects of the DSMB's scope of review and procedures will be detailed in a DSMB charter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Active comparator | Biological: rAd-IFN, Drug: Celecoxib Oral Product, Drug: GemcitabinerAd-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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and repeated every 3 weeks until disease progression/early termination [ET] |
| Control Group | Placebo comparator | Drug: Celecoxib Oral Product, Drug: GemcitabineCelecoxib (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 administered on a 21-day cycle, unless the cycle is modified due to toxicity/delay, and repeated every 3 weeks until disease progression/ET. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Patients who meet all of the following criteria will be eligible to participate in the study:
- Aged 18 years or older at the time of consent;
- Able to give informed consent;
- Has a confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (if biphasic, histology must be predominantly [50%] epithelioid). Histological diagnosis of MPM will be confirmed centrally using specimens or slides from tumor specimens obtained at the time of initial presentation or a subsequent procedure. Central confirmation of diagnosis with immunohistochemistry will be performed, and independent central confirmation will be required for study entry;
- Measurable disease, per modified Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 (see Section 7) for pleural mesothelioma;
Key exclusion criteria (37 listed)
- Patients who meet any of the following criteria will be excluded from participation in the study:
- Is "treatment-naïve" (i.e., has not received at least 1 anti-folate and platinum combination regimen);
- Has previously received 3 or more lines of systemic chemotherapeutic or immunotherapeutic treatment. Treatment that is split between pre-surgical 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;
- Has previously received treatment with gemcitabine;
- Has stage IV extrathoracic metastatic disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rAd-IFNAlso: Nadofaragene firadenovecAdenovirus-Delivered Interferon Alpha-2b | Biological | Treatment Group |
| Celecoxib Oral ProductAlso: COX II Inhibitor400 mg twice daily | Drug | Control Group, Treatment Group |
| GemcitabineAlso: Chemotherapy1250 mg/m2 administered intravenously on Days 1 and 8 of a 21-day cycle and continued every 3 weeks until disease progression/ early termination | Drug | Control Group, Treatment Group |
Primary outcome
Overall Survival
Time frame: 4 years and 8 months
Time to death (from any cause) from randomization
4 secondary outcomes
Progression Free Survival
Time frame: 4 years and 8 months
Best Response: Objective Response Rate (ORR)
Time frame: 4 years and 8 months
Best Response: Disease Control Rate (DCR)
Time frame: 4 years and 8 months
Best Response: Clinical Benefit Rate (CBR)
Time frame: 4 years and 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Sterman, MD principal investigator
NYU Langone Laura and Isaac Perlmutter Cancer Center
29 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rAd-IFN, Celecoxib Oral Product and Gemcitabine in people with Malignant Pleural Mesothelioma, run by Ferring Ventures Limited at 29 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, France, United Kingdom, Australia, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 4 years and 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.