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

Emory University

Status and phase

Enrolling

Phase 2

Conditions

Stage III Lung Cancer AJCC v8

Metastatic Lung Non-Small Cell Carcinoma

Advanced Lung Non-Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Treatments

Procedure: Magnetic Resonance Imaging

Other: Electronic Health Record Review

Biological: Cemiplimab

Biological: Atezolizumab

Drug: Diclofenac Potassium

Procedure: Computed Tomography

Procedure: Biospecimen Collection

Procedure: Positron Emission Tomography

Biological: Nivolumab

Biological: Pembrolizumab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06731270

STUDY00006572 (Other Identifier)

P30CA138292 (U.S. NIH Grant/Contract)

Winship6018-23 (Other Identifier)

NCI-2024-07760 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Treatment (diclofenac, immunotherapy)

Experimental group

Description:

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.

Treatment: