Inhaled Cromolyn Sodium in Patients With Locally Advanced Lung Cancer

Official title

An Open-Label Pilot Study Evaluating the Safety, Feasibility, and Preliminary Clinical Activity of Inhaled Cromolyn Sodium in Participants With Locally Advanced Lung Cancer

Overview

Brief Summary This prospective, open-label pilot study is designed to evaluate the safety, tolerability, feasibility, and preliminary clinical activity of inhaled cromolyn sodium administered by dry powder inhalation in participants with locally advanced lung cancer. Cromolyn sodium is an FDA-approved mast cell stabilizer with an established safety profile in respiratory disease. Increasing evidence suggests that inflammatory signaling, mast cell activation, and stromal remodeling contribute to tumor progression, immune dysregulation, and resistance to therapy within the lung tumor microenvironment. Modulation of these pathways may represent a novel therapeutic strategy in lung cancer. Approximately 5 to 10 participants with locally advanced lung cancer will receive inhaled cromolyn sodium according to the study protocol. Participants will undergo clinical assessments, safety monitoring, laboratory evaluations, and radiographic imaging in accordance with protocol-defined procedures and standard oncologic care. The primary objective of this pilot study is to evaluate the safety, tolerability, and feasibility of inhaled Cromolyn sodium administration in this patient population. Secondary objectives include exploratory assessment of radiographic response, clinical outcomes, biomarker trends, and potential signals of biological activity. Data generated from this study are intended to support the development of future clinical investigations evaluating the role of mast cell stabilization and tumor microenvironment modulation in lung cancer.

Detailed description

Scientific Background and Rationale

Lung cancer remains a leading cause of cancer-related mortality worldwide despite substantial advances in molecularly targeted therapies, immunotherapy, radiation therapy, and multimodality treatment approaches. Increasing evidence indicates that, in addition to intrinsic tumor biology, the tumor microenvironment plays a critical role in disease progression, immune evasion, therapeutic resistance, and metastatic dissemination. Consequently, there is growing interest in therapeutic strategies designed to modulate tumor-associated inflammatory and stromal processes that contribute to cancer progression.

Mast cells are resident immune cells that participate in both innate and adaptive immune responses and are increasingly recognized as important components of the tumor microenvironment. In lung cancer, mast cell infiltration has been observed within both primary tumor tissue and surrounding stromal compartments. Experimental and translational studies have suggested that mast cells may contribute to tumor-associated inflammation through the release of cytokines, chemokines, growth factors, angiogenic mediators, and proteolytic enzymes capable of influencing immune regulation, angiogenesis, extracellular matrix remodeling, and cellular proliferation.

Cromolyn sodium is an FDA-approved mast cell stabilizing agent with a long-established clinical safety profile following inhalational administration for allergic respiratory disorders. The drug inhibits mast cell degranulation and reduces the release of multiple inflammatory mediators involved in downstream immune and inflammatory signaling pathways. In addition to its effects on mast cells, preclinical investigations have suggested broader effects on inflammatory processes involving macrophages, eosinophils, neutrophils, and other immune-regulatory cell populations implicated in tumor-associated inflammation.

Preclinical studies evaluating mast cell inhibition and modulation of inflammatory signaling pathways have generated interest in the potential role of tumor microenvironment-directed therapeutic strategies in solid tumors. Although the clinical significance of these observations remains uncertain, available experimental data provide a biologically plausible rationale for exploratory clinical investigation of cromolyn sodium in lung cancer.

The pulmonary route of administration offers additional scientific rationale for evaluation in this setting. Inhaled drug delivery permits direct deposition of therapeutic agents within the respiratory tract and may facilitate local exposure within pulmonary tissues while limiting systemic drug exposure. Administration by dry powder inhaler may provide efficient pulmonary delivery and represents a practical, non-invasive method of drug administration that can be implemented in both clinical and home-based settings.

Cromolyn sodium has demonstrated a favorable safety profile during decades of clinical use. Systemic absorption following inhalation is limited, systemic toxicity is uncommon, and the drug is not associated with many of the adverse effects characteristic of conventional cytotoxic anticancer therapies. Nevertheless, the use of inhaled cromolyn sodium for the treatment of lung cancer remains investigational and has not been established as safe or effective for this indication.

Given the established clinical safety profile of inhaled cromolyn sodium, its biologic activity as a mast cell stabilizer, the emerging understanding of inflammatory and stromal mechanisms in lung cancer progression, and the potential advantages of localized pulmonary drug delivery, a pilot clinical investigation is warranted to evaluate the safety, feasibility, tolerability, and preliminary clinical activity of inhaled cromolyn sodium in participants with locally advanced lung cancer.

Safety Considerations

Participants enrolled in this study will undergo protocol-defined safety monitoring throughout the treatment and follow-up periods. Safety assessments will include evaluation of treatment-emergent adverse events, respiratory symptoms, hypersensitivity reactions, clinically significant laboratory abnormalities, and other changes in clinical status. Given the investigational nature of this treatment approach, ongoing safety surveillance will be conducted throughout study participation.

Interventions

• Drug Cromolyn Sodium
  Cromolyn sodium administered by oral inhalation using a dry powder inhaler. Treatment will be administered according to the protocol-defined dosing schedule throughout the study period.

Primary outcome measures

• Safety and Tolerability of Inhaled Cromolyn Sodium [Time frame: Up to 12 months]

Secondary outcome measures (2)

• Radiographic Tumor Response [Time frame: Baseline through 12 months]
• Feasibility of Treatment Administration [Time frame: Up to 12 months]

Eligibility criteria

Inclusion criteria

Patients with local advanced stage 3 lung cancer or lung adenocarcinoma will be eligible for the study only if they meet the following criteria:

• Provide written informed consent prior to screening.
• Male or female patients, age ≥ 18 years
• Histological- or cytological-confirmed diagnosis of Lung cancer
• Previous tumor scan location in lung

Exclusion criteria

• Treatment with another investigational drug, biological agent, or device within 4 weeks (6 weeks for biological agents) before screening or 5 half-lives of study agent, whichever is longer.
• Patients with known pericardial effusion
• Patients with active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator)
• Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device.
• Patients with any other medical condition that in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.
• Known allergy or history of serious adverse event with Cromolyn Sodium

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• In home ttreatment — Denver
• Treated at home — Denver

Publications

• Abd-Elaziz K, Oude Elberink H, Diamant Z. Improved bioavailability of cromolyn sodium using inhaled PA101 delivered via eFlow(R) nebulizer. Eur Clin Respir J. 2020 Aug 20;7(1):1809083. doi: 10.1080/20018525.2020.1809083. PMID 32944204
• Hemmati AA, Nazari Z, Motlagh ME, Goldasteh S. The role of sodium cromolyn in treatment of paraquat-induced pulmonary fibrosis in rat. Pharmacol Res. 2002 Sep;46(3):229-34. doi: 10.1016/s1043-6618(02)00122-6. PMID 12220965
• Larsson K, Larsson BM, Sandstrom T, Sundblad BM, Palmberg L. Sodium cromoglycate attenuates pulmonary inflammation without influencing bronchial responsiveness in healthy subjects exposed to organic dust. Clin Exp Allergy. 2001 Sep;31(9):1356-68. doi: 10.1046/j.1365-2222.2001.01193.x. PMID 11591185
• Blumenthal MN, Selcow J, Spector S, Zeiger RS, Mellon M. A multicenter evaluation of the clinical benefits of cromolyn sodium aerosol by metered-dose inhaler in the treatment of asthma. J Allergy Clin Immunol. 1988 Apr;81(4):681-7. doi: 10.1016/0091-6749(88)91038-x. PMID 3128589
• Dreyer CJ. Fluoridation: a review of the 1976/1977 literature. J Dent Assoc S Afr. 1979 Mar;34(3):145-54. No abstract available. PMID 397628
• Arumugam T, Ramachandran V, Logsdon CD. Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth and invasion in mouse models. J Natl Cancer Inst. 2006 Dec 20;98(24):1806-18. doi: 10.1093/jnci/djj498. PMID 17179482
• Moroni M, Porta C, Gualtieri G, Nastasi G, Tinelli C. Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients. Br J Cancer. 1996 Jul;74(2):309-11. doi: 10.1038/bjc.1996.358. PMID 8688342

Identifiers

NCT: NCT07675876 · CROM-LC-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗