NCT06731270

Diclofenac for the Treatment of Patients With Metastatic Non-small Cell Lung Cancer on Single Agent Immunotherapy

Phase II Study of Diclofenac Salvage in Patients Metastatic Non-Small Cell Lung Cancer With Early Signs of Progression on Single Agent PD(L)-1 Blockade

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the clinical benefit rate of concomitant diclofenac potassium (diclofenac) and single agent checkpoint blockade. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of concomitant diclofenac and single agent checkpoint blockade. II. To evaluate the efficacy of concomitant diclofenac and single agent checkpoint blockade in NSCLC. EXPLORATORY OBJECTIVES: I. To evaluate the change in immunophenotype in circulating CD8 T cells following initiation of diclofenac oral therapy in patients who show early sings of progression on single agent immunotherapy for advanced lung cancer. II. To investigate the role of PD-L1 expression status in response to the addition of diclofenac daily oral therapy in patients who show early sings of progression on single agent immunotherapy for advanced lung cancer. III. To evaluate the role of serum lactic acid levels in determining dose exposure to diclofenac. IV. To evaluate the change in circulating immune parameters (CD4 T cells and B cells) with the addition of diclofenac to single agent immunotherapy. V. To evaluate the role of the tumor microenvironment at the time of diagnosis on efficacy. OUTLINE: Patients receive diclofenac orally (PO) twice daily (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 computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) on study. After completion of study treatment, patients are followed up every 12 weeks for up to 1 year.

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

Interventions

Type	Name	Description
BIOLOGICAL	Atezolizumab	Given atezolizumab
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
BIOLOGICAL	Cemiplimab	Given cemiplimab
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Diclofenac Potassium	Given PO
OTHER	Electronic Health Record Review	Ancillary studies
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Nivolumab	Given nivolumab
BIOLOGICAL	Pembrolizumab	Given pembrolizumab
PROCEDURE	Positron Emission Tomography	Undergo PET

Timeline

• Start date: 2025-04-09
• Primary completion: 2027-01-01
• Completion: 2028-01-01
• First posted: 2024-12-12
• Last updated: 2026-02-12

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study