Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Osteosarcoma

Sarcoma

Neoplasm Metastasis

Neoplasm, Residual

Neoplastic Processes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Patients undergo pulmonary suffusion consisting of cisplatin via infusion. Patients the undergo metastasectomy. Beginning 4-8 weeks, patients with unresectable sarcoma may receive chemotherapy.

Isolated Chemotherapeutic Lung Perfusion

Metastasectomy

Todd L. Demmy

Todd L Demmy

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.

PRIMARY OBJECTIVES:

I. To assess the safety of chemotherapy isolated to the pulmonary circulation by determining the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of each chemotherapy agent. (Phase I) II. To determine the rate of local recurrences in patients receiving pulmonary suffusion, compared to historical controls in patients with completely resected pulmonary metastases (unilateral and bilateral disease). (Phase II)

SECONDARY OBJECTIVES:

I. To determine the local and systemic toxicities associated with pulmonary suffusion. (Phase I) II. To determine whether suffusion improves metastatic control by suppressing progression of microscopic metastases to new lesions assessable by imaging (Phase I) III. To determine disease-free survival (DFS) in patients receiving pulmonary suffusion compared to historical controls, in patients with completely resected pulmonary metastases (unilateral and bilateral disease). (Phase II)

EXPLORATORY OBJECTIVES:

I. To evaluate the pulmonary suffusion-associated changes in local tumor microenvironment (TME) and potential of suffusion as an immune modulation enhancement. (Phase II) II. To determine overall survival (OS) in patients receiving pulmonary suffusion compared to historical controls, in patients with completely resected pulmonary metastases (unilateral and bilateral disease). (Phase II) III. To compare histology of tumor samples with previously resected specimens with attention to biomarkers of systemic immune recognition in patients eligible for repeat suffusion. (Phase II) IV. To obtain tumor and systemic immune biomarkers including cytokine activations for correlation with clinical responses. (Phase II) V. To correlate local control with biomarker for tissue effect from chemotherapy (including tissue levels of platinum, alkaline phosphatase \[ALP\]). (Phase II) VI. To correlate local disease control with tumor biomarker for metastasis (circulating \[circ\] ribonucleic acid \[RNA\], micro \[mi\]RNA). (Phase II)

OUTLINE:

Patients undergo pulmonary suffusion consisting of cisplatin via infusion. Patients then undergo metastasectomy. Patients found to have unresectable sarcoma may receive chemotherapy within 4-8 weeks of metastasectomy.

After completion of study treatment, patients are followed up for 3 months for one year and then every 6 months for up to 5 years.

Pulmonary Suffusion in Controlling Minimal Residual Disease in Patients With Sarcoma or Colorectal Metastases

Phase I/ II Study of Pulmonary Suffusion to Control Minimal Residual Disease in Resectable or Ablatable Sarcoma or Colorectal Pulmonary Metastases

The association between lung injury and response and survival outcomes will be evaluated using logistic and Cox regression models.

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.

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.

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.

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.

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.

Assessed using the NCI CTCAE v5.0. Will be summarized by grade within each arm using frequencies and relative frequencies.

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.

Spots Global Cancer Trial Database for isolated chemotherapeutic lung perfusion