Comprehensive Multimodal Prehabilitation Alone or in Combination With Planned Neoadjuvant Therapy in High-risk Patients Prior to Elective Major Cancer Surgery
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Rate of morbidity-free survival
研究概览
简要总结
In this 2-arm, non-randomized, phase II trial, the investigators will evaluate the efficacy and safety of comprehensive multimodal prehabilitation (CMMP) alone or in combination with planned neoadjuvant (NAT) in pre-frail/frail patients with probable/proven pancreaticobiliary, ovarian, kidney, or bladder cancer prior to elective major cancer surgery (EMCS).
详细描述
This is a 2-arm, non-randomized, phase II trial evaluating the efficacy and safety of comprehensive multimodal prehabilitation (CMMP) alone or in combination with planned/off-protocol neoadjuvant therapy (NAT) in high-risk (pre-frail/frail) patients with probable/proven pancreaticobiliary, ovarian, renal, or bladder cancer prior to elective major cancer surgery (EMCS, including pancreatectomy [N=38 in each study arm], cytoreduction [N=12 in each study arm], radical nephrectomy [N=12 in each study arm], or total cystectomy [N=12 in each study arm]; respectively and accounting for a potential 20% dropout rate). The two study arms are independent; within arm (i.e., across cancer and/or procedure types) and between arm comparison will not be performed. The CMMP intervention combines motivational interviewing (MI) with nutritional prehabilitation, inspiratory muscle training, and physical prehabilitation (aerobic exercises and strength/resistance training). Approximately 74 high-risk, male or female patients, 18 years of age or older, will be enrolled in Arm 1 (CMMP alone) and 74 similar patients will be enrolled in Arm 2 (CMMP & planned NAT).
The primary endpoints are postoperative morbidity-free survival and safety after CMMP. The secondary endpoints are preoperative functional status/fitness; completion of planned preoperative therapy (in Arm 2 only); preoperative/postoperative health-related quality-of -life (HRQOL); and receipt of intended (adjuvant) oncologic therapy (RIOT). Additional secondary endpoints will include postoperative morbidity/healthcare utilization and 2-year overall survival (OS) and disease-free survival (DFS; in patients with proven [histologically confirmed] cancer) after CMMP. The tertiary endpoints are nutritional status and body composition after CMMP.
Exploratory analyses using baseline/pre-CMMP and post-CMMP peripheral blood samples, as well as baseline/pre-CMMP (clinical diagnostic biopsy) and post-CMMP (EMCS specimen) tumor samples will include (but not be limited to) correlates of response to CMMP including as peripheral immune modulation, as well as (in patients with proven cancer) changes to the tumor microenvironment (TME: vasculature, hypoxia, and immune cell infiltration) and pathologic response (in Arm 1 patients who did not receive NAT prior to study entry).
Patients in Arm 1 (CMMP alone) will receive (at least 3) weekly cycles of CMMP between study registration and Preoperative Reassessment. Patients in Arm 2 (CMMP & planned NAT) will receive (at least 3) weekly cycles of CMMP during receipt of planned/off-protocol NAT between study registration and Preoperative Reassessment. Patients will be provided with ready access to videos explaining the subcomponents of the CMMP intervention. Throughout the CMMP intervention, weekly automated assessments of adherence to the CMMP intervention and assessments for AEs/SAEs will be conducted electronically (via text/email using a text-enabled Research Electronic Data Capture [REDCap] database/system) and/or by study staff (in-person or by email/telephone).
At the Preoperative Reassessment, impact of the CMMP intervention on relevant intermediate endpoints will be evaluated, including, nutritional status, body composition (muscle mass), respiratory muscle function, muscular (grip) strength, functional capacity, functional status/fitness, HRQOL, and ECOG performance status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patients are eligible for entry into the study (First Registration) only if ALL of the following criteria apply. No exceptions or waivers will be granted for patients who do not meet the eligibility criteria.
- •Signed informed consent form.
- •Age ≥18 years at time of signing informed consent form.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 per the treating cancer surgeon (Arm 1, Neoadjuvant therapy) or per both the treating cancer surgeon and the medical and/or radiation oncologists (Arm 2, no neoadjuvant therapy).
- •Pre-frail or frail (based on the Fried Frailty Phenotype
- •Probable or proven (histologically confirmed) pancreaticobiliary/periampullary (i.e., pancreatic cancer, cholangiocarcinoma, duodenal cancer, or ampullary cancer), ovarian cancer, kidney cancer, or bladder cancer based on central pathological review at Houston Methodist Hospital.
- •Clinically non-metastatic (stage I-III) or metastatic (IV) disease.
- •Technically resectable disease (no significant vascular, neural, or bony involvement and potential to safely achieve R0 resection) and potentially medically fit for EMCS per the treating cancer surgeon (surgical oncologist/HBP surgeon, gynecologic oncologist, or urologic oncologist).
- •Tentatively scheduled to undergo elective pancreatectomy (open or minimally invasive pancreaticoduodenectomy or open distal pancreatectomy) for pancreaticobiliary/periampullary cancer, elective surgical cytoreduction for ovarian cancer, elective open radical nephrectomy for kidney cancer, or elective (open or minimally invasive) total cystectomy for bladder cancer by one of the study MPI or Co-Is > 28 days after trial registration.
- •Neoadjuvant therapy group only: Completed planned NAT (if any) at least 2 weeks prior to Study Registration.
- •No neoadjuvant therapy group only: Medically fit and planned to receive NAT per the treating medical and/or radiation oncologist.
- •Ability to comply with the CMMP intervention and study assessments as per protocol, in the MPI's judgment.
- •Willing and able to consume a lactose-free, whey protein supplement (if not allergic to milk protein/soy and no history of galactosemia), marine protein supplement (if not allergic to marine protein/shellfish), or pea protein supplement (if not allergic to pea protein).
- •Willing to provide tissue and blood specimens as per protocol.
- •For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
- •Access to a smart phone (personally or via caretaker who resides with the patient).
- •Understands, speaks, and reads English.
排除标准
- •Patients are NOT eligible for entry into the study (First Registration) only ANY of the following criteria apply. No exceptions or waivers will be granted for patients who do not meet the eligibility criteria.
- •Difficulty or inability to hear and/or understand loud speech and sounds.
- •Unable to eat by mouth (e.g., tube feed dependent, on total parenteral nutrition, etc.)
- •Oxygen dependent (or rest and/or with exertion).
- •Significant cardiovascular disease (such as New York Heart Association (NYHA) Functional Classification III or IV, unstable angina, unstable arrhythmia, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of trial treatment.
- •Dependence on mobility device for ambulation other than a cane (e.g., crutches, walker, wheelchair).
- •Active brain metastasis or leptomeningeal disease.
- •Active bone metastasis and/or recent bone fracture.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). NOTE: Patients with indwelling catheters (e.g., PleurX) are allowed
- •Planned receipt of investigational therapy/treatment (other than the protocol-mandated CMMP intervention) during the trial treatment.
- •Major procedure/surgery within 12 weeks prior to initiation of trial treatment that would prevent the patient from complying with the CMMP intervention and study assessments as per protocol, in the MPI's judgment.
- •Active physical/mental condition or personal/social circumstance that would prevent the patient from complying with the CMMP intervention and study assessments as per protocol, in the MPI's judgment.
研究组 & 干预措施
CMMP intervention
Participants will receive the CMMP intervention, which includes motivational interviewing, nutritional prehabilitation (nutritional assessment/counseling and protein supplementation), inspiratory muscle training, and physical prehabilitation (aerobic and strength/resistance training) for at least 3 weeks prior to elective major cancer surgery.
干预措施: Comprehensive multimodal prehabilitation (CMMP) (Other)
Planned neoadjuvant therapy/CMMP intervention
Participants will receive the CMMP intervention (in conjunction with planned, off-protocol neoadjuvant therapy), which includes motivational interviewing, nutritional prehabilitation (nutritional assessment/counseling and protein supplementation), inspiratory muscle training, and physical prehabilitation (aerobic and strength/resistance training) for at least 3 weeks prior to elective major cancer surgery.
干预措施: Comprehensive multimodal prehabilitation (CMMP) (Other)
结局指标
主要结局
Rate of morbidity-free survival
时间窗: At 30 days postoperatively
Percentage of patients alive without any postoperative complications (as defined by the American College of Surgeons National Surgical Quality Improvement Program {ACS NSQIP\]) in each study arm.
Rates of adverse events and serious adverse events
时间窗: From study enrollment to the time of planned, off-protocol, preoperative re-evaluation by the participant's primary cancer surgeon (approximately 1 month after enrollment in Arm 1 and 2-3 months after enrollment in Arm 2 ).
Percentage of patients with adverse events and serious adverse events (AEs/SAEs; as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v5.0) during receipt of CMMP in each study arm.
次要结局
- Rate of improvement in preoperative functional status/fitness(At the time of planned, off-protocol, preoperative re-evaluation by the participant's primary cancer surgeon (approximately 1 month after enrollment in Arm 1 and 2-3 months after enrollment in Arm 2).)
- Rate of completion of planned preoperative therapy(At the time of planned, off-protocol, preoperative re-evaluation by the participant's primary cancer surgeon (approximately 1 month after enrollment in Arm 1 and 2-3 months after enrollment in Arm 2).)
- Rate of postoperative pulmonary complications (PPCs)(At 30 days postoperatively)
- Health-related quality of life (HRQOL)(At the time of planned, off-protocol, preoperative re-evaluation by the participant's primary cancer surgeon (approximately 1 month after enrollment in Arm 1 and 2-3 months after enrollment in Arm 2) and at 30, 60, and 90 days postoperatively.)
- Postoperative rate of receipt of intended oncologic therapy (RIOT)(At 30, 60, and 90 days postoperatively)
- Rate of postoperative discharge to home(At the time of hospital discharge (approximately 7 days postoperatively))
- Postoperative length of stay(At the time of hospital discharge (approximately 7 days postoperatively))
- Disease-free survival (DFS)(2 years after EMCS)
- Rate of hospital readmission(At 30, 60, and 90 days postoperatively)
- Overall survival (OS)(2 years after EMCS)
研究者
Nestor Esnaola
Professor of Surgery
The Methodist Hospital Research Institute