Phase I/ II Study of Pulmonary Suffusion to Control Minimal Residual Disease in Resectable or Ablatable Sarcoma or Colorectal Pulmonary Metastases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Incidence of local toxicities (Phase I)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Isolated Chemotherapeutic Lung Perfusion (Procedure)
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.
干预措施: Metastasectomy (Procedure)
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.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Incidence of local toxicities (Phase I)
时间窗: 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)
时间窗: Up to 5 years
Local recurrence (Phase II)
时间窗: 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 II)
时间窗: Up to 5 years
Assessed using the NCI CTCAE v5.0. Will be summarized by grade within each arm using frequencies and relative frequencies
次要结局
- 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)
- Incidence of local and systemic toxicities (Phase II)(Up to 5 years)
- Local recurrence within the treated (suffusion) and untreated lungs for patients with bilateral disease (Phase II)(At 2 years)
- Incidence of local and systemic toxicities (Phase I)(Up to 5 years)
- Rate of successful Chemotherapy delivery(Periprocedural)