Recruiting
Phase 2

Diclofenac

Sponsor:

Emory University

Code:

NCT06731270

Conditions

Advanced Lung Non-Small Cell Carcinoma

Metastatic Lung Non-Small Cell Carcinoma

Stage III Lung Cancer AJCC v8

Stage IV Lung Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Atezolizumab

Biospecimen Collection

Cemiplimab

Computed Tomography

Diclofenac Potassium

Study Details

Brief summary:

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.

Conditions

Advanced Lung Non-Small Cell Carcinoma

Metastatic Lung Non-Small Cell Carcinoma

Stage III Lung Cancer AJCC v8

Stage IV Lung Cancer AJCC v8

Study ID

NCT06731270

Start date

Apr 9, 2025

Status verified date

Feb, 2026

Completion date

Jan 1, 2028

Anticipated

Primary completion date

Jan 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Capable of signing informed consent
  • Age ≥ 18 years at time of study entry
  • Stage III or IV pathologically proven NSCLC with advanced or metastatic disease, currently on treatment with an Food and Drug Administration (FDA) approved single agent monoclonal antibody inhibiting the PD(L)-1 pathway (pembrolizumab, atezolizumab, nivolumab, or cemiplimab) for a minimum of 12 weeks

  • May include frontline single agent immune checkpoint inhibitors (ICI), maintenance single agent ICI after chemo-ICI, or subsequent line therapy
  • Radiographic evidence of clinical progression as determined by the treating physician, not warranting immediate change of therapy. Progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria is not required. This can include mixed response, will need at least one growing lesion. Exposure to PD1 inhibitor for at least 12 weeks will minimize the risk of pseudo-progression
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy of ≥ 26 weeks
  • Absolute neutrophil count (ANC) ≥ 1,000 cell/mm\^3
  • Platelets ≥ 100,000 cells/mm\^3
  • Hemoglobin ≥ 8 gm/dL
  • Creatinine clearance ≥ 45 ml/ml
  • Bilirubin ≤ 1.5 x institutional upper limit of normal

  • Bilirubin must be ≤ 3 x institutional upper limit of normal in patients with documented Gilbert's syndrome
  • Serum glutamic oxaloacetic transaminase (SGOT) / serum gluatmic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal
  • Ability to take oral medications
  • Willingness and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria:

  • Concurrent enrollment in another clinical study, unless it is non-therapeutic
  • Prophylactic or therapeutic anticoagulation therapy including but not limited to: warfarin, heparin, low molecular weight heparin, or direct oral anticoagulants, including: dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa)
  • Treatment within the previous 6 weeks or planned initiation of bevacizumab
  • Abnormal markers of coagulation as measured by international normalized ratio (INR) > 2
  • Contraindication for NSAID therapy including: chronic aspirin therapy for coronary artery disease (CAD), cerebrovascular accident (CVA), or other indication, uncontrolled gastrointestinal ulcerative disease, known bleeding diathesis, known allergy or hypersensitivity to NSAIDS, advanced renal disease, uncontrolled hypertension, known seizure disorder or others
  • Female of childbearing potential unwilling or unable to use 2 methods of contraception, detailed in protocol
  • Uncontrolled intercurrent illness
  • History of another primary malignancy with exceptions noted in protocol
  • History of active primary immunodeficiency or active infection including tuberculosis, hepatitis B, hepatitis C
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of diclofenac. There are exceptions to this criterion
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of study medications
  • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (diclofenac, immunotherapy)

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.

Interventions

Atezolizumab

Given atezolizumab

Biospecimen Collection

Undergo blood sample collection

Cemiplimab

Given cemiplimab

Computed Tomography

Undergo CT

Diclofenac Potassium

Given PO

Electronic Health Record Review

Ancillary studies

Magnetic Resonance Imaging

Undergo MRI

Nivolumab

Given nivolumab

Pembrolizumab

Given pembrolizumab

Positron Emission Tomography

Undergo PET

Primary outcome measure

  • Clinical benefit rate (CBR) [ Time Frame: At 12 weeks ]

Central Contacts and Locations

Central contacts

Kajona McCall

404-778-5087kajohna.mccall@emory.edu

Locations

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Jennifer W Carlisle

404-778-2304Jennifer.W.Carlisle@emory.edu

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Jennifer W. Carlisle

404-778-2304Jennifer.W.Carlisle@emory.edu

Principal Investigator:

Jennifer W. Carlisle

More Information

Sponsor

Emory University

Last update posted

Feb 12, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2026-02-12.