rAd-IFN + Celecoxib + Gemcitabine for Mesothelioma

(INFINITE Trial)

Recruiting at 42 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

53 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination rAd-IFN, Celecoxib, and Gemcitabine for treating mesothelioma?

Research shows that combining COX-2 inhibitors like Celecoxib with immunotherapy can enhance the immune response against tumors, potentially leading to tumor shrinkage in mesothelioma. Additionally, studies suggest that interferons, like rAd-IFN, can boost the effectiveness of chemotherapy drugs such as Gemcitabine, making this combination a promising approach for treating mesothelioma. ^{1 2 3 4 5}

Is the combination of rAd-IFN, Celecoxib, and Gemcitabine safe for humans?

Celecoxib and Gemcitabine have been studied for safety in humans. Celecoxib, a nonsteroidal anti-inflammatory drug, has shown potential antitumor effects in mesothelioma models, while Gemcitabine has been evaluated in clinical trials for mesothelioma, indicating some level of safety data exists for these drugs in humans. ^{4 5 6 7 8}

What makes the rAd-IFN + Celecoxib + Gemcitabine treatment unique for mesothelioma?

This treatment is unique because it combines rAd-IFN, which boosts the immune system to fight cancer, with Celecoxib, a drug that reduces inflammation and may enhance the immune response, and Gemcitabine, a chemotherapy drug. This combination aims to improve outcomes by targeting the cancer through multiple mechanisms, including reducing the tumor's ability to suppress the immune system and directly attacking cancer cells. ^{2 4 5 9 10}

What is the purpose of this trial?

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: 1. Treatment group: rAd-IFN + Celecoxib followed by Gemcitabine 2. 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

Research Team

Daniel Sterman, MD

Principal Investigator

NYU Langone Laura and Isaac Perlmutter Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP). [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

[A case report of disseminated malignant mesothelioma of peritoneum responding remarkably to thalidomide, celecoxib, vinorelbine and CDDP]. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Use of cyclooxygenase-2 inhibition to enhance the efficacy of immunotherapy. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Piroxicam and cisplatin in a mouse model of peritoneal mesothelioma. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of the nonsteroidal anti-inflammatory agent celecoxib on malignant mesothelioma chemoprevention. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The role of gemcitabine in the treatment of malignant mesothelioma. [2022]

10. Ireland 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). [2022]