Pulmonary Suffusion in Controlling Minimal Residual Disease in Patients With Soft Tissue or Bone Sarcoma Metastatic to the Lungs
Study Details
Study Description
Brief Summary
This phase I/II trial studies the side effects of pulmonary suffusion in controlling minimal residual disease in patients with soft tissue or bone sarcoma 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- 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:
- To determine the local and systemic toxicities associated with pulmonary suffusion. (Phase
-
- 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:
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Cisplatin
Given via infusion
Other Names:
Procedure: Isolated Chemotherapeutic Lung Perfusion
Undergo pulmonary suffusion
Other Names:
Procedure: Metastasectomy
Undergo metastasectomy
|
Outcome Measures
Primary Outcome Measures
- Incidence of local toxicities (Phase I) [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) [Up to 5 years]
- Local recurrence (Phase II) [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.
Secondary Outcome Measures
- Incidence of local and systemic toxicities (Phase I) [Up to 5 years]
Assessed using the NCI CTCAE v5.0.
- Disease-free survival (Phase II) [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) [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) [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.
Other Outcome Measures
- Lung injury (% reduction of spirometry and differential reduction by quantitative perfusion scan) (Phase II) [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) [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) [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.
Eligibility Criteria
Criteria
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
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Forced expiratory volume in 1 second (FEV1) >= 50% predicted
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Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% predicted
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Vital capacity (VC) >= 50% predicted
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Ambulatory and resting oxygen (O2) saturation > 88%
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Six minute walk >= 50 % of the expected distance
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Surgeon and interventional radiologist affirmation that suffusion is technically feasible
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Borg Dyspnea scale (modified) < 5
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Control of the primary sarcoma tumor as determined by clinical assessment per standard of care
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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 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
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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
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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
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Allergy, intolerance, or other serious reaction to cisplatin
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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
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Pregnant or nursing female participants
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Unwilling or unable to follow protocol requirements
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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
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Severe peripheral neuropathy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
Sponsors and Collaborators
- Roswell Park Cancer Institute
Investigators
- Principal Investigator: Todd L Demmy, Roswell Park Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- i 70818
- NCI-2019-02940
- i 70818