Comprehensive pre-surgery conditioning, with or without planned preoperative cancer therapy, before major abdominal or pelvic cancer operations.

Comprehensive Multimodal Prehabilitation Alone or in Combination With Planned Neoadjuvant Therapy in High-risk Patients Prior to Elective Major Cancer Surgery

This trial will test whether a comprehensive prehabilitation program, given alone or with planned neoadjuvant therapy, helps pre-frail or frail adults with pancreatic, ovarian, kidney, or bladder cancer better tolerate major cancer surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 148 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Methodist Hospital Research Institute (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07050771 on ClinicalTrials.gov

What this trial studies

This is a two-arm, non-randomized phase II trial enrolling high-risk (pre-frail or frail) adults with probable or proven pancreaticobiliary, ovarian, renal, or bladder cancer who are scheduled for elective major cancer surgery. Participants receive a comprehensive multimodal prehabilitation program (motivational interviewing, nutritional optimization, inspiratory muscle training, aerobic and resistance exercise), either alone or combined with planned neoadjuvant therapy. Each arm will enroll approximately 74 patients across specified procedures (including pancreatectomy, cytoreduction, radical nephrectomy, and cystectomy), and the arms are analyzed independently without direct between-arm comparisons. Primary endpoints are postoperative morbidity-free survival and safety, with secondary endpoints including preoperative functional status, pre/postoperative quality of life, completion of planned therapy (arm 2), and receipt of intended adjuvant therapy.

Who should consider this trial

Good fit: Adults (≥18) with probable or proven pancreaticobiliary, ovarian, kidney, or bladder cancer who are pre-frail or frail (per Fried criteria), have ECOG performance status 0–2, and are scheduled for elective major cancer surgery are ideal candidates.

Not a fit: Patients who are not pre-frail/frail, are medically unfit for surgery, cannot participate in or complete the prehabilitation program, or who have rapidly progressive disease that precludes planned surgery are unlikely to benefit.

Why it matters

Potential benefit: If successful, the program could reduce postoperative complications and improve functional recovery and quality of life after major cancer surgery for frail patients.

How similar studies have performed: Prior prehabilitation studies in other surgical populations have shown improved fitness and fewer complications, but comprehensive multimodal prehabilitation combined with planned neoadjuvant therapy in these high‑risk cancer groups is relatively untested.

Eligibility criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Where this trial is running

Houston, Texas

• Houston Methodist Neal Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Nestor Esnaola, M.D. — Houston Methodist Neal Cancer Center
• Study coordinator: Darrel Cleere, BSN,RN,CCRP

Conditions Hepatopancreaticobiliary Malignancy; Ovarian Cancer; Kidney Cancers; Bladder Cancer