Metastatic Bone SarcomaPhase 1/2NCT03965234
Pulmonary Suffusion in Controlling Minimal Residual Disease in Patients With Sarcoma or Colorectal Metastases
A Phase 1/2 study testing Cisplatin, Isolated Chemotherapeutic Lung Perfusion and Metastasectomy in people with Metastatic Bone Sarcoma and Metastatic Malignant Neoplasm in the Lung, run by Roswell Park Cancer Institute at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Bone Sarcoma, Metastatic Malignant Neoplasm in the Lung, Metastatic Soft Tissue Sarcoma
- What is being tested?
- Cisplatin, Isolated Chemotherapeutic Lung Perfusion and Metastasectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jul 2020to 25 May 2030
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Tumors metastatic to the lungs that are the focus of this protocol specifically:
- Colorectal carcinoma
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Hemoglobin > 8.0 g/L
- Neutrophils > 1,500 uL
- Platelets >= 100,000 uL
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- Creatinine clearance >= 30 mL/min
- Clinically diagnosed 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 stereotactic body radiation therapy (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
- Pulmonary function judged by the surgeon to be sufficient to tolerate the planned pulmonary metastasectomy. Testing is not required but generally is performed clinically and will be left to the discretion of the treating surgeon. The following are not required but serve as guidelines since they were used to determine eligibility for the Phase I protocol: EV1 >= 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 and resection or ablation of all nodules is technically feasible
- 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/consulting 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
Who cannot join
- 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.
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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, 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Kenneth Seastedt, MD, 716-845-8675, Kenneth.Seastedt@roswellpark.org
Kenneth Seastedt
About this study
Official title: Phase I/ II Study of Pulmonary Suffusion to Control Minimal Residual Disease in Resectable or Ablatable Sarcoma or Colorectal Pulmonary Metastases
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.
The Phase 1 portion of the study has been completed.
Read the 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) of each chemotherapy agent. (Phase I)
- 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)
- To support the safety of chemotherapy isolated to the pulmonary circulation by evaluating adverse events at an oxaliplatin dose of 12.75 mg/m2 (15% systemic), as established by completion of Phase I in this trial.
SECONDARY OBJECTIVES:
- To determine the local and systemic toxicities associated with pulmonary suffusion. (Phase I)
- To determine whether suffusion improves metastatic control by suppressing progression of microscopic metastases to new lesions assessable by imaging (Phase I)
- 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)
- To continue to refine the surgical and interventional techniques of suffusion within the framework established by the clinical trial (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 for one year and then every 6 months for up to 5 years.
- Conditions
- Metastatic Bone Sarcoma, Metastatic Malignant Neoplasm in the Lung, Metastatic Soft Tissue Sarcoma, Metastatic Unresectable Sarcoma, Resectable Sarcoma, Colorectal Cancer
- Being tested
- Cisplatin, Isolated Chemotherapeutic Lung Perfusion, Metastasectomy
- Medical subject headings
- Bone Neoplasms, Sarcoma, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given via infusion
Isolated Chemotherapeutic Lung PerfusionProcedure or surgery
Also called isolated lung perfusion
Undergo pulmonary suffusion
MetastasectomyProcedure or surgery
Undergo metastasectomy
| Study group | Role | What they receive |
|---|---|---|
| Prevention (cisplatin, metastasectomy) | Experimental | Patients undergo pulmonary suffusion consisting of cisplatin via infusion. Patients the undergo metastasectomy. Beginning 4-8 weeks, patients with unresectable sarcoma may receive chemotherapy. Receives: Drug: Cisplatin; Procedure: Isolated Chemotherapeutic Lung Perfusion; Procedure: Metastasectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Recommended phase II dose (Phase I)
Measured: Up to 5 years
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.
Measured: From resection until local recurrence in the suffused lung or last clinic follow-up, assessed up to 2 years
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
Measured: Up to 5 years
Secondary outcomes (4)
Incidence of local and systemic toxicities (Phase I)
Assessed using the NCI CTCAE v5.0.
Measured: Up to 5 years
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.
Measured: From suffusion until recurrence (local or distant), death due to or related to disease, or last follow-up, assessed up to 2 years
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.
Measured: At 2 years
Rate of successful Chemotherapy delivery
Measured by blood draws for drug levels
Measured: Periprocedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2019
- Study start16 Jul 2020
- Primary completion25 May 2029 (estimated)
- Study completion25 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Bone SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kenneth Seastedt, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03965234
- Sponsor's protocol ID
- i 70818
- Other IDs
- NCI-2019-02940, i 70818
- Status last verified
- Aug 2026
- First submitted
- 22 May 2019
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No