Diclofenac + Immunotherapy for Lung Cancer

Recruiting at 1 trial location

Overseen By Kajona McCall

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must be taking: PD(L)-1 inhibitors

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Active infection, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 33

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of adding diclofenac, a common anti-inflammatory drug, to immunotherapy for treating non-small cell lung cancer (NSCLC) that has metastasized. Researchers aim to determine if diclofenac can reduce inflammation and enhance immunotherapy's ability to target and kill cancer cells. Participants should have spreading NSCLC, be on a specific immunotherapy for at least 12 weeks, and show signs of cancer progression without needing an immediate change in treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

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

The trial does not specify if you need to stop all current medications, but you cannot be on anticoagulation therapy or have used immunosuppressive medication within 14 days before starting diclofenac. You must also not have received a live vaccine within 30 days before the trial.

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

A previous study showed that diclofenac, a type of pain reliever, is generally safe and well-tolerated. Used worldwide since 1974, it is considered as safe as ibuprofen, which many people commonly use. Most people do not experience serious side effects.

Research suggests that diclofenac might also aid in cancer treatment by affecting cancer cell growth. When combined with cancer-fighting drugs like pembrolizumab, atezolizumab, nivolumab, or cemiplimab, diclofenac could enhance their effectiveness. However, while diclofenac is generally safe, all medications can have side effects. Participants should discuss any concerns with the doctors conducting the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about combining diclofenac with immunotherapy for lung cancer because it offers a novel approach to treatment. While standard care options like pembrolizumab, atezolizumab, nivolumab, or cemiplimab are effective on their own, adding diclofenac is thought to potentially enhance the immune response against cancer cells. Diclofenac, a common anti-inflammatory drug, may help reduce inflammation in the tumor environment, allowing the immune system to work more effectively. This combination could lead to improved outcomes for patients by potentially increasing the effectiveness of existing immunotherapies.

What evidence suggests that diclofenac combined with immunotherapy might be an effective treatment for metastatic NSCLC?

Research has shown that combining diclofenac, a common anti-inflammatory drug, with immunotherapy might help treat non-small cell lung cancer (NSCLC) that has spread. In this trial, participants will receive diclofenac along with standard-of-care immunotherapy, which may include pembrolizumab, atezolizumab, nivolumab, or cemiplimab. Studies have found that patients with NSCLC who took NSAIDs (a group of drugs that includes diclofenac) along with immunotherapy lived longer. Diclofenac reduces inflammation, which might assist the body’s immune system in fighting cancer more effectively. Immunotherapy drugs like pembrolizumab and nivolumab already help the immune system attack cancer cells. Adding diclofenac could enhance this treatment's effectiveness against cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Jennifer Carlisle, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with metastatic non-small cell lung cancer who are currently on single-agent immunotherapy. Participants should not have any health conditions that would interfere with the study or pose additional risks.

Inclusion Criteria

Life expectancy of ≥ 26 weeks

Creatinine clearance ≥ 45 ml/min

Serum glutamic oxaloacetic transaminase (SGOT) / serum gluatmic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal

Exclusion Criteria

Concurrent enrollment in another clinical study, unless it is non-therapeutic

I am not using two forms of birth control.

Abnormal markers of coagulation as measured by international normalized ratio (INR) > 2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive diclofenac orally twice daily and standard of care immunotherapy on day 1 of each cycle, with cycles repeating every 21 or 28 days

12 weeks

Every 21 or 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 1 year

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diclofenac

Trial Overview The effectiveness of diclofenac, an anti-inflammatory drug, in enhancing the tumor-killing ability of existing immunotherapies like pembrolizumab, atezolizumab, nivolumab, or cemiplimab is being tested in this phase II trial.

How Is the Trial Designed?

Group I: Treatment (diclofenac, immunotherapy) Experimental Treatment 10 Interventions

Patients receive diclofenac PO BID and standard of care immunotherapy with pembrolizumab, atezolizumab, nivolumab or cemiplimab on day 1 of each cycle. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT, PET, or MRI on study.

Diclofenac is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Voltaren for:

• Ankylosing Spondylitis
• Aseptic Necrosis
• Back Pain
• Chronic Pain
• Frozen Shoulder
• Headache
• Migraine
• Muscle Pain
• Osteoarthritis
• Pain
• Period Pain
• Rheumatoid Arthritis
• Sciatica
• Spondyloarthritis

Approved in European Union as Voltaren for:

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis
• Migraine
• Pain
• Dysmenorrhea

Approved in Canada as Voltaren for:

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis
• Migraine
• Pain
• Dysmenorrhea

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Diclofenac (VOLTAREN) is effective for various conditions treated with NSAIDs, showing good tolerability and a favorable balance between COX-2 and COX-1 inhibition, which may reduce side effects.

The drug is available in multiple forms and has a long history of use, but caution is advised for patients at risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Voltaren--the gold standard]. Babić-Naglić, D.[2013]

In a four-week double-blind trial involving 182 patients with rheumatoid arthritis, diclofenac sodium (Voltaren) showed comparable effectiveness to indomethacin in improving clinical symptoms, while the placebo group showed no significant changes.

Voltaren was associated with fewer central nervous system side effects compared to indomethacin, although both medications had similar gastrointestinal side effects, indicating a potentially safer profile for Voltaren.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclophenax sodium (Voltaren) in rheumatoid arthritis: a double-blind comparison with indomethacin and placebo. Kirchheiner, B., Trang, L., Wollheim, FA.[2013]

A phase I/II trial involving 46 patients with untreated advanced non-small cell lung cancer (NSCLC) demonstrated that the combination of carboplatin, nab-paclitaxel, and pembrolizumab is a safe and effective treatment, achieving a median overall survival of 15.4 months.

The study found a 35% overall response rate and a median progression-free survival of 5.6 months, indicating that this regimen can provide a durable benefit for patients, regardless of their PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Gentzler, RD., Mohindra, NA., Jalal, SI., et al.[2023]

Diclofenac sodium has been used worldwide since 1974, and extensive safety data indicate it is safer and better tolerated than aspirin, with safety comparable to ibuprofen and naproxen.

Clinical trials in the U.S. show that patients taking diclofenac (150 mg daily) experienced fewer adverse reactions compared to those on other nonsteroidal anti-inflammatory drugs, except for naproxen at 500 mg daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Worldwide safety experience with diclofenac. Catalano, MA.[2019]

Recent advancements in pharmacogenomics have led to the development of novel agents for treating non-small cell lung cancer adenocarcinoma, emphasizing the importance of testing for specific mutations like EGFR and ALK in clinical practice.

Immunotherapy, particularly with agents like nivolumab and pembrolizumab, has emerged as a promising treatment for advanced non-small cell lung cancer, although monitoring for adverse effects is crucial during patient follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. Zarogoulidis, P., Chinelis, P., Athanasiadou, A., et al.[2020]

Diclofenac sodium, the active ingredient in Voltaren, has been shown to effectively reduce inflammation and pain in animal models, demonstrating its analgesic and anti-inflammatory properties.

The compound has a favorable safety profile compared to other nonsteroidal anti-inflammatory drugs, as indicated by its tolerability metrics, and it works by inhibiting cyclo-oxygenase and lipoxygenase pathways, which are crucial in the inflammatory response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of diclofenac sodium. Scholer, DW., Ku, EC., Boettcher, I., et al.[2019]

Data from over 100,000 patients indicate that diclofenac is safe and well-tolerated, with adverse effects being infrequent and generally mild, especially when compared to placebo and other NSAIDs.

Long-term use of diclofenac (over a year) has shown no significant increase in adverse effects for older patients compared to younger patients, making it a reliable option for treating various rheumatic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Worldwide clinical safety experience with diclofenac. Willkens, RF.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06731270

NCT06731270 | Diclofenac for the Treatment of Patients ... This phase II trial tests how well diclofenac works in treating patients non-small cell lung cancer (NSCLC) that may have spread from where it first started ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525730423000013

The Association of Improved Overall Survival with NSAIDs ... This study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS.

3. trialx.com trialx.com/clinical-trials/listings/299199/diclofenac-for-the-treatment-of-patients-with-metastatic-non-small-cell-lung-cancer-on-single-agent-immunotherapy/

Diclofenac for the Treatment of Patients With ... This phase II trial tests how well diclofenac works in treating patients non-small cell lung cancer (NSCLC) that may have spread from where it ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/1759-7714.15294

Impact of concurrent medications on the outcome ... The treatment outcomes of patients with advanced non-small cell lung cancer (NSCLC) have significantly improved with the introduction of immune ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07760

Diclofenac for the Treatment of Patients with Metastatic ... This phase II trial tests how well diclofenac works in treating patients non-small cell lung cancer (NSCLC) that may have spread from where it first started ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4720497/

Repurposing Drugs in Oncology (ReDO)—diclofenac as an ... Of note results in non-small cell lung cancer (NSCLC) showed a statistically significant impact of pre-operative DCF on the risk of distant metastases (HR = 0. ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844023104117

The relationship between nonsteroidal anti-inflammatory ... Our results revealed that overall NSAID use was associated with a decreased risk of breast, CNS, esophageal, gastric, head and neck, liver, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9138099/

Diclofenac: A Nonsteroidal Anti-Inflammatory Drug Inducing ... Our study suggests that microtubule destabilization by diclofenac induces cancer cell death via compromised spindle assembly checkpoints and increased ROS.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.12055

The safety and efficacy of diclofenac sodium suppository as ... This study demonstrated that diclofenac sodium suppository was an effective treatment option for managing breakthrough pain in patients with persistent cancer ...

10. withpower.com withpower.com/trial/diclofenac-immunotherapy-for-lung-cancer-8548a

Diclofenac + Immunotherapy for Lung Cancer Diclofenac has been used worldwide since 1974 and is generally considered safe and well-tolerated, with safety data showing it is comparable to ibuprofen and ...