Non-Small Cell Lung Cancer
Conditions
Brief summary
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
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.
Interventions
DRUGcis-diamminedichloroplatinum
Cisplatin delivered bronchoscopically at the time of diagnosis of NSCLC
Sponsors
University of Vermont
Johnson & Johnson
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Dose Limiting Toxicity | Within 2 weeks of delivery | Adverse events as defined using the Common Terminology Criteria for Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response | Assessed on the surgical resection specimen, performed within 30 days of bronchoscopic delivery | Evaluation of the tissue response to the drug |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORC. Matthew Kinsey, MD, MPH
University of Vermont
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 1 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
None listed