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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03965234
• Other study ID #: i 70818
• Secondary ID: NCI-2019-02940i
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 16, 2020
• Est. completion date: May 25, 2030

Study information

• Verified date: March 2024
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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) 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: May 25, 2030
• Est. primary completion date: May 25, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Tumors metastatic to the lungs that are the focus of this protocol specifically:
• Soft tissue sarcoma
• Osteosarcoma
• Colorectal carcinoma
• 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 metastases(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) Given the emergence of other acceptable options to destroy lung metastases such as SBRT or microwave ablation, a hybrid approach to eliminate all sites of disease will be permitted; however, supplemental approaches should be delayed, if possible, until after the 30 day post-suffusion endpoint
• 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 affirmation that suffusion is technically feasible
• Borg Dyspnea scale (modified) < 5
• Control of the primary tumor as determined by clinical assessment per standard of care; may include stable tumor status of primary tumor and other metastases, in the clinical judgement of the PI/Physician.
• 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:

• 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 chemotherapy drugs that may be used in the procedure
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Pulmonary metastases unable to be completely resected or ablated based on pre-registration review of imaging by a thoracic surgeon or proceduralist.
• Any additional condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug or the suffusion technique, may include uncontrolled intercurrent illness and other conditions that, in the judgement of the PI/Physician, would limit compliance with the study requirements and have safety concerns
• Received an investigational agent within 30 days prior to enrollment
• Severe peripheral neuropathy

Related Conditions & MeSH terms

• Colorectal Cancer
• Metastatic Bone Sarcoma
• Metastatic Malignant Neoplasm in the Lung
• Metastatic Soft Tissue Sarcoma
• Metastatic Unresectable Sarcoma
• Neoplasm, Residual
• Neoplasms
• Resectable Sarcoma
• Sarcoma

Intervention

Drug:
• Cisplatin
Given via infusion

Procedure:
• Isolated Chemotherapeutic Lung Perfusion
Undergo pulmonary suffusion
• Metastasectomy
Undergo metastasectomy

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Lung injury (% reduction of spirometry and differential reduction by quantitative perfusion scan) (Phase II)	The association between lung injury and response and survival outcomes will be evaluated using logistic and Cox regression models.	Up to 5 years
Other	Immune markers (Phase II)	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.	Up to 5 years
Other	Overall survival (Phase II)	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.	Up to 5 years
Primary	Incidence of local toxicities (Phase I)	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.	Up to 2 years
Primary	Recommended phase II dose (Phase I)		Up to 5 years
Primary	Local recurrence (Phase II)	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.	From resection until local recurrence in the suffused lung or last clinic follow-up, assessed up to 2 years
Secondary	Incidence of local and systemic toxicities (Phase I)	Assessed using the NCI CTCAE v5.0.	Up to 5 years
Secondary	Disease-free survival (Phase II)	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.	From suffusion until recurrence (local or distant), death due to or related to disease, or last follow-up, assessed up to 2 years
Secondary	Incidence of local and systemic toxicities (Phase II)	Assessed using the NCI CTCAE v5.0. Will be summarized by grade within each arm using frequencies and relative frequencies.	Up to 5 years
Secondary	Local recurrence within the treated (suffusion) and untreated lungs for patients with bilateral disease (Phase II)	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.	At 2 years