Diclofenac for the Treatment of Patients with Metastatic Non-small Cell Lung Cancer on Single Agent Immunotherapy
18 Years and older, Male and Female
Winship6018-23 (primary)
NCI-2024-07760
STUDY00006572
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.
Objectives
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.
Eligibility
- 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, which 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
Treatment Sites in Georgia
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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