This phase I/II trial studies the side effects of pulmonary suffusion in controlling minimal residual disease in patients with sarcoma or colorectal carcinoma that has spread to the lungs. Pulmonary suffusion is a minimally invasive delivery of chemotherapeutic agents like cisplatin to lung tissues. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pulmonary suffusion may also be useful in avoiding later use of drugs by vein that demonstrate no effect on tumors when delivered locally.
The Phase 1 portion of the study has been completed.
Colorectal carcinoma
Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
Hemoglobin > 8.0 g/L
Neutrophils > 1,500 uL
Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Allergy, intolerance, or other serious reaction to chemotherapy drugs that may be used in the procedure
Pregnant or nursing female participants
Single group
Cisplatin
DrugGiven via infusion
Isolated Chemotherapeutic Lung Perfusion
Procedure/SurgeryUndergo pulmonary suffusion
Metastasectomy
Procedure/SurgeryUndergo metastasectomy
Incidence of local toxicities (Phase I)
Dose limiting toxicities (DLTs) will be defined based on the rate of drug-related grade 3-5 adverse events. These will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
Recommended phase II dose (Phase I)
Local recurrence (Phase II)
Will be treated as bivariate time-to-event data. Freedom from local recurrence will be summarized using standard Kaplan-Meier methods and the 2-year local recurrence-free rate will be estimated with a 90% confidence interval calculated using Greenwood's formula.
Incidence of local and systemic toxicities (Phase II)
Assessed using the NCI CTCAE v5.0. Will be summarized by grade within each arm using frequencies and relative frequencies
Incidence of local and systemic toxicities (Phase I)
Assessed using the NCI CTCAE v5.0.
Disease-free survival (Phase II)
Will be summarized using standard Kaplan-Meier methods, where estimates of the median survival and 2-year survival rates will be obtained with 90% confidence intervals.
Local recurrence within the treated (suffusion) and untreated lungs for patients with bilateral disease (Phase II)
Will be compared between the suffused and non-suffused lungs using McNemar?s test. A 90% confidence interval about the difference in local recurrence rates will also be obtained.
Rate of successful Chemotherapy delivery
Measured by blood draws for drug levels
Lung injury (% reduction of spirometry and differential reduction by quantitative perfusion scan) (Phase II)
The association between lung injury and response and survival outcomes will be evaluated using logistic and Cox regression models.
Immune markers (Phase II)
Will be correlated to primary endpoints. The cytokine activation, tumor, immune, and stress related biomarkers will be summarized using the appropriate descriptive statistics. The association between overall response and the biomarkers will be evaluated using logistic regression models. The association between time-to-event outcomes (freedom from recurrence and survival) and the biomarkers will be evaluated using Cox regression models. All model assumptions will be verified graphically and fit using Firth's method.
Overall survival (Phase II)
Will be compared to historical controls. Will be summarized using standard Kaplan-Meier methods, where estimates of the median survival and 2-year survival rates will be obtained with 90% confidence intervals.
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