Pulmonary Suffusion in Controlling Minimal Residual Disease in Patients With Soft Tissue or Bone Sarcoma Metastatic to the Lungs
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03965234|
Recruitment Status : Recruiting
First Posted : May 28, 2019
Last Update Posted : December 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Bone Sarcoma Metastatic Malignant Neoplasm in the Lung Metastatic Soft Tissue Sarcoma Metastatic Unresectable Sarcoma Resectable Sarcoma||Drug: Cisplatin Procedure: Isolated Chemotherapeutic Lung Perfusion Procedure: Metastasectomy||Phase 1 Phase 2|
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)
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)
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)
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/ II Study of Pulmonary Suffusion to Control Minimal Residual Disease in Resectable Sarcoma Pulmonary Metastases|
|Actual Study Start Date :||July 16, 2020|
|Estimated Primary Completion Date :||May 25, 2029|
|Estimated Study Completion Date :||May 25, 2030|
Experimental: Prevention (cisplatin, metastasectomy)
Patients undergo pulmonary suffusion consisting of cisplatin via infusion. Patients the undergo metastasectomy. Beginning 4-8 weeks, patients with unresectable sarcoma may receive chemotherapy.
Given via infusion
Procedure: Isolated Chemotherapeutic Lung Perfusion
Undergo pulmonary suffusion
Other Name: isolated lung perfusion
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03965234
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Todd L. Demmy 716-845-8675 email@example.com|
|Principal Investigator: Todd L. Demmy|
|Principal Investigator:||Todd L Demmy||Roswell Park Cancer Institute|