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

Trial Summary

What is the purpose of this trial?

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 (primary site) to other places in the body (metastatic) on single agent immunotherapy. Diclofenac, a type of non-steroidal anti-inflammatory (NSAID), blocks the body's production of a substance that causes inflammation and may decrease tumor growth and improve the effectiveness of immunotherapy. Immunotherapy with pembrolizumab, atezolizumab, nivolumab or cemiplimab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving diclofenac may kill more tumor cells in patients with metastatic NSCLC on single agent immunotherapy.

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.

What data supports the effectiveness of the drug Diclofenac when used with immunotherapy for lung cancer?

Research suggests that some non-steroidal anti-inflammatory drugs (NSAIDs), like diclofenac, may enhance the effectiveness of cancer treatments. Specifically, diclofenac has shown to increase the effectiveness of certain chemotherapy drugs in lung cancer cells, which might suggest potential benefits when combined with immunotherapy. ^{1 2 3 4 5}

Is diclofenac generally safe for human use?

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 naproxen. It has been tested in over 100,000 patients, with side effects being infrequent and usually mild, and it is considered one of the safest drugs of its kind for treating various conditions. ^{6 7 8 9 10}

How does the drug Diclofenac combined with immunotherapy differ from other lung cancer treatments?

This treatment is unique because it combines Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) known for its ability to induce apoptosis (programmed cell death) in cancer cells, with immunotherapy, which is a novel approach for advanced lung cancer. This combination may enhance the anti-cancer effects by targeting different pathways involved in tumor growth. ^{4 8 10 11 12}

Research Team

Jennifer Carlisle, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

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.

I have not started or received bevacizumab in the last 6 weeks.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Impact of Concomitant Medication Administered at the Time of Initiation of Nivolumab Therapy on Outcome in Non-small Cell Lung Cancer. [2022]

2. England 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. [2023]

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

The Association of Improved Overall Survival with NSAIDs in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Anticancer effects of non-steroidal anti-inflammatory drugs against cancer cells and cancer stem cells. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Diclophenax sodium (Voltaren) in rheumatoid arthritis: a double-blind comparison with indomethacin and placebo. [2013]

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

Worldwide safety experience with diclofenac. [2019]

8. Croatia pubmed.ncbi.nlm.nih.gov

[Voltaren--the gold standard]. [2013]

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

Worldwide clinical safety experience with diclofenac. [2019]

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

Pharmacology of diclofenac sodium. [2019]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Diclofenac sodium: a review of its pharmacological properties and therapeutic use in rheumatic diseases and pain of varying origin. [2018]

12. England pubmed.ncbi.nlm.nih.gov

The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti-inflammatory drugs (NSAIDs). [2022]