• Incidence of local toxicities (Phase I) [ Time Frame: Up to 2 years ]
  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) [ Time Frame: Up to 5 years ]
• Local recurrence (Phase II) [ Time Frame: From resection until local recurrence in the suffused lung or last clinic follow-up, assessed up to 2 years ]
  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 I) [ Time Frame: Up to 5 years ]
  Assessed using the NCI CTCAE v5.0.
• Disease-free survival (Phase II) [ Time Frame: From suffusion until recurrence (local or distant), death due to or related to disease, or last follow-up, assessed up to 2 years ]
  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.
• Incidence of local and systemic toxicities (Phase II) [ Time Frame: Up to 5 years ]
  Assessed using the NCI CTCAE v5.0. Will be summarized by grade within each arm using frequencies and relative frequencies.
• Local recurrence within the treated (suffusion) and untreated lungs for patients with bilateral disease (Phase II) [ Time Frame: At 2 years ]
  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.

• Lung injury (% reduction of spirometry and differential reduction by quantitative perfusion scan) (Phase II) [ Time Frame: Up to 5 years ]
  The association between lung injury and response and survival outcomes will be evaluated using logistic and Cox regression models.
• Immune markers (Phase II) [ Time Frame: Up to 5 years ]
  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) [ Time Frame: Up to 5 years ]
  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.

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). (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 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 and then every 6 months for up to 5 years.

• Metastatic Bone Sarcoma
• Metastatic Malignant Neoplasm in the Lung
• Metastatic Soft Tissue Sarcoma
• Metastatic Unresectable Sarcoma
• Resectable Sarcoma

• Drug: Cisplatin
  Given via infusion
  Other Names:

  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
• Procedure: Isolated Chemotherapeutic Lung Perfusion
  Undergo pulmonary suffusion
  Other Name: isolated lung perfusion
• Procedure: Metastasectomy
  Undergo metastasectomy

Inclusion Criteria:

• Soft tissue or bone sarcoma metastatic to the lungs
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Hemoglobin > 8.0 g/L
• Granulocytes > 1,500 uL
• Platelets >= 100,000 uL
• Creatinine clearance >= 30 mL/min
• Clinically diagnosed resectable sarcoma lung metastasis(while preregistration histologic or cytologic confirmation is desirable, this may not be required in clinical scenarios where a biopsy may not change the need to resect suspicious lung nodules or the biopsy itself poses a risk for tumor seeding. In such cases, the diagnosis will be supported by rapid pathologic evaluations intraoperatively before proceeding with Suffusion)
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Forced expiratory volume in 1 second (FEV1) >= 50% predicted
• Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% predicted
• Vital capacity (VC) >= 50% predicted
• Ambulatory and resting oxygen (O2) saturation > 88%
• Six minute walk >= 50 % of the expected distance
• Surgeon and interventional radiologist affirmation that suffusion is technically feasible
• Borg Dyspnea scale (modified) < 5
• Control of the primary sarcoma tumor by imaging performed =< 1 month prior to study enrollment
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Use of home oxygen
• 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 cisplatin
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac conditions ( ike congestive heart failure, angina pectoris, and arrhythmias that are unstable or refractory to management) or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any additional condition which in the Investigator?s opinion deems the participant an unsuitable candidate to receive study drug or the suffusion technique
• Received an investigational agent within 30 days prior to enrollment
• Severe peripheral neuropathy