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

NCT06731270 | Recruiting Phase 2 FDA Drug

• 4 other identifiers: STUDY00006572NCI-2024-07760Winship6018-23P30CA138292
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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

Metastatic Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Advanced Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate (CBR)

  CBR will be defined as complete response, partial response, and/or stable disease. Clinical response will be assessed using Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 criteria. Clinical benefit rate will be reported as a proportion, with an exact 80% confidence interval estimated using the Clopper-Pearson method.

  At 12 weeks

Secondary Outcomes (5)

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study treatment

• Objective response rate (ORR)

  At 12 weeks

• Progression-free survival (PFS)

  From initiation of treatment to progression or death up to 1 year

• Overall survival (OS)

  From diagnosis to death from any cause up to 1 year

• Duration of response (DOR)

  From the date of first response to the date of the first progressive disease or death due to any cause up to 1 year

Study Arms (1)

Treatment (diclofenac, immunotherapy)

EXPERIMENTAL

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.

Biological: Atezolizumab; Procedure: Biospecimen Collection; Biological: Cemiplimab; Procedure: Computed Tomography; Drug: Diclofenac Potassium; Other: Electronic Health Record Review; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Biological: Pembrolizumab; Procedure: Positron Emission Tomography

Interventions

Atezolizumab BIOLOGICAL

Given atezolizumab

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Treatment (diclofenac, immunotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (diclofenac, immunotherapy)

Cemiplimab BIOLOGICAL

Given cemiplimab

Also known as: Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN 2810, REGN-2810, REGN2810

Treatment (diclofenac, immunotherapy)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (diclofenac, immunotherapy)

Diclofenac Potassium DRUG

Given PO

Also known as: Cambia, Cataflam, CGP 45840B, Zipsor

Treatment (diclofenac, immunotherapy)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (diclofenac, immunotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (diclofenac, immunotherapy)

Nivolumab BIOLOGICAL

Given nivolumab

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (diclofenac, immunotherapy)

Pembrolizumab BIOLOGICAL

Given pembrolizumab

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, QL2107, SCH 900475, SCH-900475, SCH900475

Treatment (diclofenac, immunotherapy)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (diclofenac, immunotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

atezolizumab; Specimen Handling; cemiplimab; Diclofenac; Magnetic Resonance Spectroscopy; Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Spectrum Analysis; Chemistry Techniques, Analytical; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jennifer W Carlisle

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kajona McCall

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 12, 2024
• Study Start: April 9, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (2)