rAd-IFN + Celecoxib + Gemcitabine for Mesothelioma

(INFINITE Trial)

Not currently recruiting at 46 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ferring Ventures Limited

Must not be taking: Lithium, Interferons, others

Disqualifiers: Stage IV metastasis, Cardiac disease, Auto-immune, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: Until disease progression or early termination

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for Malignant Pleural Mesothelioma (MPM), a cancer affecting the lung lining. Researchers are testing whether a therapy involving a virus-delivered protein (rAd-IFN), combined with the drugs celecoxib and gemcitabine, can improve survival compared to using celecoxib and gemcitabine alone. This trial targets individuals who have tried one or two other treatments, including a specific chemotherapy combination, without success. For those with MPM who have not seen results from previous treatments, this trial might be suitable. As a Phase 3 trial, it represents the final step before potential FDA approval, offering access to a promising treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific time requirements for stopping certain treatments before starting the trial, such as a 21-day gap for cytotoxic chemotherapy and a 30-day gap for monoclonal antibodies. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rAd-IFN, when administered directly into the space around the lungs, is generally safe. One study found that repeated doses in this area are well-tolerated, indicating no major safety issues.

Celecoxib, a drug commonly used for pain and inflammation, has been adapted for cancer treatment. It appears safe in this new role and may help slow tumor growth.

Gemcitabine is a well-known chemotherapy drug. Studies indicate it is effective, and its side effects are generally manageable for patients with pleural mesothelioma. It has been used in various combinations and is considered safe.

These findings suggest that using rAd-IFN, celecoxib, and gemcitabine together is likely safe based on past research. However, individual reactions can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of rAd-IFN with celecoxib and gemcitabine for treating mesothelioma because it introduces a novel mechanism of action. Unlike traditional therapies such as surgery, radiation, and chemotherapy, which primarily aim to remove or directly kill cancer cells, rAd-IFN is a gene therapy that boosts the body's immune response against the tumor. This approach has the potential to enhance the effectiveness of existing chemotherapy drugs like gemcitabine. Additionally, the use of celecoxib, an anti-inflammatory drug, may help reduce side effects and improve the overall treatment experience. By integrating these components, this treatment regimen offers a promising alternative to the current standard of care.

What evidence suggests that this trial's treatments could be effective for Mesothelioma?

Research has shown that rAd-IFN, one of the treatments in this trial, may help fight mesothelioma by boosting the body's immune system when administered directly into the chest. Early studies suggest this method can increase levels of interferon, a protein that aids the immune system in attacking cancer cells. Celecoxib, another drug in this trial, may slow tumor growth and enhance the immune system's response to cancer. Gemcitabine, also included in this trial, is already used for mesothelioma and has been found to help patients live longer without their cancer worsening. This trial will compare the combination of these treatments to improve overall survival and manage mesothelioma more effectively. ^{1 4 6 7 8}

Who Is on the Research Team?

Daniel Sterman, MD

Principal Investigator

NYU Langone Laura and Isaac Perlmutter Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Malignant Pleural Mesothelioma who've had 1-2 prior treatments, including an anti-folate and platinum regimen. They must be able to undergo intrapleural therapy, have a life expectancy of at least 12 weeks, and be in good physical condition (ECOG status 0 or 1). Women must not be pregnant and agree to contraception; men also need to use contraception.

Inclusion Criteria

The doctor thinks you have about 12 weeks to live.

I am fully active or restricted in physically strenuous activity but can do light work.

I am a woman who cannot have children because I am postmenopausal or have been surgically sterilized.

Exclusion Criteria

You have had problems digesting galactose or glucose in the past.

My cancer has spread beyond my chest to other parts of my body.

My blood pressure is very high and not well-managed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive rAd-IFN, celecoxib, and gemcitabine or celecoxib and gemcitabine alone

Until disease progression or early termination

Regular visits every 3 weeks for gemcitabine administration

Follow-up

Participants are monitored for survival and safety every 6 months for up to 5 years

60 months

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Celecoxib Oral Product
• Gemcitabine
• rAd-IFN

Trial Overview

The study tests rAd-IFN given through the chest cavity along with Celecoxib and Gemcitabine versus just Celecoxib and Gemcitabine. The goal is to see if adding rAd-IFN improves survival. Patients are randomly assigned to either the treatment group receiving all three drugs or the control group receiving only two.

How Is the Trial Designed?

Group I: Treatment Group Active Control 3 Interventions

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 \[ET\]

Group II: Control Group Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Ferring Ventures Limited

Lead Sponsor

Trials

1

Recruited

50+

Trizell Ltd

Lead Sponsor

Trials

1

Recruited

50+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a phase II study involving 50 patients with unresectable malignant mesothelioma, the combination of gemcitabine and cisplatin showed a modest overall response rate of 12%, with one complete response and five partial responses, primarily in patients with specific tumor histologies.

The treatment resulted in a median overall survival of 10 months and a median progression-free survival of 6 months, with an acceptable safety profile, although 16 patients experienced Grade 4 toxicities, mainly hematologic, and there were no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin in unresectable malignant mesothelioma of the pleura: a phase II study of the Southwest Oncology Group (SWOG 9810). Kalmadi, SR., Rankin, C., Kraut, MJ., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/14961568/

Preclinical evaluation of the nonsteroidal anti-inflammatory ...

Celecoxib was more efficient in inhibiting MM cell growth than acetylsalicylic acid (10(-6) M-10(-2) M), indometacin (10(-6) M-10(-2) M) and the COX-2 inhibitor ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2939552/

COX-2 inhibition improves immunotherapy & decreases MDSCs

We conclude that celecoxib is a powerful tool to improve dendritic cell-based immunotherapy and is associated with a reduction in the numbers and suppressive ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03710876

Study Details | NCT03710876 | Efficacy & Safety of rAd-IFN ...

This study will evaluate intrapleural administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in combination with Celecoxib and Gemcitabine in ...

4.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/abs/10.1002/ijc.11710

Preclinical evaluation of the nonsteroidal anti‐inflammatory ...

Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res 2000 ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S016950021400347X

Effect of NSAIDS and COX-2 inhibitors on the incidence ...

Conclusion. We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this ...

6.

mayo.edu

mayo.edu/research/clinical-trials/cls-20469678

A Study to Evaluate the Effectiveness and Safety of rAd-IFN ...

A Study to Evaluate the Effectiveness and Safety of rAd-IFN Administered With Celecoxib and Gemcitabine in Patients With Malignant Pleural Mesothelioma.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9488560/

Drug repurposing in malignant pleural mesothelioma

Among its anticancer effects, celecoxib inhibits cell cycle progression [67], induces apoptosis [68], inhibits angiogenesis and metastasis [69], and increases ...

8.

clinconnect.io

clinconnect.io/trials/NCT03710876

Efficacy & Safety of rAd-IFN Administered With Celecoxib

This clinical trial is studying a new treatment approach for patients with Malignant Pleural Mesothelioma (MPM), a type of cancer affecting the lining of the ...