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Pulmonary Suffusion in Controlling Minimal Residual Disease in Patients With Soft Tissue or Bone Sarcoma Metastatic to the Lungs

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ClinicalTrials.gov Identifier: NCT03965234
Recruitment Status : Recruiting
First Posted : May 28, 2019
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute

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
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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

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:
  • 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




Primary Outcome Measures :
  1. 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.

  2. Recommended phase II dose (Phase I) [ Time Frame: Up to 5 years ]
  3. 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.


Secondary Outcome Measures :
  1. Incidence of local and systemic toxicities (Phase I) [ Time Frame: Up to 5 years ]
    Assessed using the NCI CTCAE v5.0.

  2. 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.

  3. 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.

  4. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Biopsy or cytologically proven resectable or unresectable sarcoma lung metastasis
  • 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 like congestive heart failure, angina pectoris, and arrhythmias that are unstable or refractory to managemnet, 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

Information from the National Library of Medicine

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


Locations
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United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Todd L. Demmy    716-845-8675    todd.demmy@roswellpark.org   
Principal Investigator: Todd L. Demmy         
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
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Principal Investigator: Todd L Demmy Roswell Park Cancer Institute
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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT03965234    
Other Study ID Numbers: i 70818
NCI-2019-02940 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
i 70818 ( Other Identifier: Roswell Park Cancer Institute )
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: September 11, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Sarcoma
Neoplasms
Neoplasm, Residual
Osteosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Cisplatin
Antineoplastic Agents