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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Atezolizumab
  Given atezolizumab
• Процедура Biospecimen Collection
  Undergo blood sample collection
• Биопрепарат Cemiplimab
  Given cemiplimab
• Процедура Computed Tomography
  Undergo CT
• Препарат Diclofenac Potassium
  Given PO
• Другое Electronic Health Record Review
  Ancillary studies
• Процедура Magnetic Resonance Imaging
  Undergo MRI
• Биопрепарат Nivolumab
  Given nivolumab
• Биопрепарат Pembrolizumab
  Given pembrolizumab
• Процедура Positron Emission Tomography
  Undergo PET

Первичные конечные точки

• Clinical benefit rate (CBR) [Срок оценки: At 12 weeks]

Вторичные конечные точки (5)

• Incidence of adverse events (AEs) [Срок оценки: Up to 30 days after last dose of study treatment]
• Objective response rate (ORR) [Срок оценки: At 12 weeks]
• Progression-free survival (PFS) [Срок оценки: From initiation of treatment to progression or death up to 1 year]
• Overall survival (OS) [Срок оценки: From diagnosis to death from any cause up to 1 year]
• Duration of response (DOR) [Срок оценки: From the date of first response to the date of the first progressive disease or death due to any cause up to 1 year]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Emory University Hospital Midtown — Atlanta
• Emory University Hospital/Winship Cancer Institute — Atlanta

Идентификаторы

NCT: NCT06731270 · STUDY00006572 · NCI-2024-07760 · STUDY00006572 · Winship6018-23 · P30CA138292

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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