Intratumoral Cisplatin for Resectable NSCLC

Study Overview
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Brief Summary
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PRIMARY OBJECTIVE: To identify the maximum tolerated dose (MTD) of intratumoral cisplatin, delivered during a single bronchoscopy with cone-beam CT confirmation, in a dose escalation protocol DESIGN: 3+3 dose escalation.

Detailed Description
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Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. Even for early stage disease, the rate of recurrence following surgical resection is as high as 50%. Although neoadjuvant therapy, administered before surgery, for early stage lung cancer is associated with a survival benefit, it is rarely used due to the systemic toxicity of intravenous (IV) cytotoxic chemotherapy. IV immunotherapies are also being evaluated in combination with systemic therapies in the neoadjuvant setting. However, only a minority of patients respond to immunotherapy. One of the most common reasons for failure of immunotherapy is lack of presentation of tumor antigens to the immune system, a problem that may be potentially addressed with cytotoxic agents. Over the last several years, case series have demonstrated the feasibility and safety of delivering cisplatin directly into lung tumors. Given the current knowledge of safety and tolerability of intratumoral cisplatin, coupled with the potential to achieve immune priming that may help address systemic micrometastases, the investigators postulate that intratumoral cisplatin will be well-tolerated, and potentially effective, neoadjuvant therapy for patients with early stage, resectable, non-small cell lung cancer.

Official Title
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A Phase 1 Trial of Intratumoral Cisplatin for Early Stage, Resectable, Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: cis-diamminedichloroplatinum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Eastern Cooperative Oncology Group performance status 0 or 1 Patients must have adequate organ and marrow function as defined below: Leukocytes ≥3,000/microliter Platelets ≥100,000/microliter Total bilirubin ≤ institutional upper limit of normal (ULN) Aspartate aminotransferase /Alanine aminotransferase ≤3 × institutional upper limit of normal Creatinine ≤ institutional ULN Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial Have known or suspected clinical stage I-IIb NSCLC after computed tomography (CT) and/or positron emission tomography at time of enrollment Presence of a target lesion with a minimum volume of 1.0 cm3, (approximately1.2 cm in diameter) and ≤ 5.0 cm in diameter Agreement from a cardiothoracic surgeon, following review of past medical history, medications, pulmonary function testing, and CT scan that patient is likely to be a surgical candidate and that, after considering known possible adverse events, delivery of intratumoral cisplatin is unlikely to adversely affect surgical feasibility Rapid on-site cytopathologic examination (ROSE) performed during the procedure returns likely NSCLC (per the determination of a trained, attending, cytopathologist). No research procedures will be performed if ROSE is non-diagnostic A CT scan of the chest (with or without contrast) within 1 month of the screening visit Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Use of an investigational agent within 30 days of the screening visit IV chemotherapy within the 30 days of the screening visit Pregnancy/lactation (pregnancy test to be performed by pre-op as part of standard of care for women of child-bearing age as defined by University of Vermont Medical Center Policy History of prior radiation to the study lesion History of allergic reaction to cisplatin or its derivatives Patients with uncontrolled intercurrent illness Physician determination that patient would not be appropriate for study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intratumoral Cisplatin Arm<br>Single arm approach. There is no comparator or placebo group. Cisplatin will be administered directly into a non-small cell lung cancer, following imaging verification and pathologic diagnosis, during a single bronchoscopic procedure. | Drug: cis-diamminedichloroplatinum<br>* Cisplatin delivered bronchoscopically at the time of diagnosis of NSCLC<br>* Other names: cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of dose limiting toxicity | Adverse events as defined using the Common Terminology Criteria for Adverse Events | Within 2 weeks of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic response | Evaluation of the tissue response to the drug | Assessed on the surgical resection specimen, performed within 30 days of bronchoscopic delivery | 
| Blood biomarker panel | Includes serum cytokine analysis, mass cytometry for inflammatory cells, and complete blood count | Assessed from blood drawn on day of bronchoscopy and day of surgical resection | 
| Tissue biomarker panel | Includes evaluation of cellular constituents and sequencing of cells present in tissue | Assessed from tissue obtained on day of bronchoscopy and day of surgical resection |