Nutrition Therapy in Improving Immune System in Patients With Bladder Cancer That Can Be Removed by Surgery

Phase 3

Active, not recruiting

Conditions: Bladder Carcinoma

Interventions: Other: Laboratory Biomarker Analysis
Dietary Supplement: Nutritional Intervention
Other: Placebo Administration
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Registration Number: NCT03757949

Lead Sponsor: SWOG Cancer Research Network

Brief Summary: This phase III trial studies how well nutrition therapy works in improving immune system in patients with bladder cancer that can be removed by surgery. Improving nutrition before and after surgery may reduce the infections and other problems that sometimes occur after surgery.

Detailed Description: PRIMARY OBJECTIVE:

I. To compare the impact of consuming perioperative specialized immune-modulating drinks (SIM, Impact Advanced Recovery, Nestle) to oral nutrition supplement control drinks (ONS, Oral Nutrition Control, Nestle) on post-operative complications (any versus \[vs.\] none) within 30 days after scheduled radical cystectomy (RC).

SECONDARY OBJECTIVES:

I. To assess whether SIM use compared to ONS reduces late-phase post-operative complications within 90 days after scheduled RC.

II. To assess whether SIM use compared to ONS reduces infections. III. To assess whether SIM use compared to ONS reduces skeletal muscle wasting. IV. To assess whether SIM use compared to ONS reduces high grade post-operative complications.

V. To assess whether SIM use compared to ONS reduces readmission rates. VI. To assess whether SIM use compared to ONS improves quality of life. VII. To assess whether SIM use compared to ONS improves disease-free survival after surgery and overall survival.

TERTIARY OBJECTIVES:

I. To assess the impact of SIM use on the expansion of myeloid-derived suppressor cells.

II. To assess the impact of SIM use on pro-inflammatory cytokines and neutrophil: lymphocyte ratios.

III. To assess the impact of SIM use on post-operative arginine deficiency and amino acid metabolism.

IV. To explore the association of dietary intake variables (nutrition status, calories, protein, and immune-enhancing factors) and study outcomes.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To describe the microbiome of the gut in patients undergoing radical cystectomy and urinary diversion prior to initiation of immunonutrition or a nutrition control.

II. To define the microbiome change in patients undergoing radical cystectomy and urinary diversion after they have received blinded immunonutrition or control nutritional supplement.

III. To correlate cancer treatments, postoperative complications (specifically infections) and nutritional status with microbiome composition.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive SIM orally (PO) thrice daily (TID) on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.

ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.

After completion of study, patients are followed up at 2, 30, and 90 days, and at 6, 9, 12, 18, 24, and 36 months after surgery.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 203

Inclusion Criteria

Patients must have a tissue diagnosis of primary cell carcinoma of the bladder by transurethral resection of bladder tumor (TURBT) or partial cystectomy; patients may not have any evidence of unresectable disease or metastatic disease as assessed by exam under anesthesia or imaging (computed tomography [CT], magnetic resonance imaging [MRI], positron-emission tomography [PET])
There must be plans for the cystectomy to be performed within 28 calendar days after registration
Surgery must be planned to be performed under pre-approved, study-specific surgical guidelines
Patients must have completed any neoadjuvant chemotherapy or immunotherapy (intravesical or systemic) >= 14 calendar days prior to registration and any toxicities resolved to at least grade 2
Patients may have a history of radiation therapy; radiation therapy must have been completed >= 180 days prior to registration
Patients may have a history of prior partial cystectomy; prior partial cystectomy must have been completed at least 180 days prior to registration
Patients with planned adjuvant chemotherapy within 90 days after radical cystectomy will not be eligible
Patients must be able to swallow liquid and have no refractory nausea, vomiting, malabsorption, or significant small bowel resection that would preclude adequate absorption; patients on tube feeding are not eligible
Patients must have their baseline nutrition status assessed using the Scored Patient-Generated Subjective Global Assessment (PG-SGA) by a clinician or licensed healthcare practitioner (trained physician, nurse, or dietician) within 14 days prior to registration and must not have a global category rating of stage C (severely malnourished)
Patients must not have galactosemia
Patients must not have known active viral infections such as human immunodeficiency virus (HIV) or hepatitis, as these chronic viral infections may cause cachexia and immunodeficiency and thus alter the biology regarding the study endpoints
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years; prostate cancer found at cystectomy would not be considered a prior malignancy
Patients must not be pregnant or nursing as the conditions preclude candidacy for radical cystectomy
Patients must consent and be willing to have specimens collected and submitted
Patients must be offered the opportunity to participate in additional specimen banking
Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Patients must consent and provide their telephone contact information for four 24-hour dietary recall phone interviews to be conducted by staff at the Exercise, Diet, Genitourinary, & Endocrinology Laboratory (EDGE) Research Laboratory
Patients must be able to understand and speak English and/or Spanish because the dietary recall phone interviews will only be conducted in English or Spanish

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	Laboratory Biomarker Analysis	ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm I (SIM)	Laboratory Biomarker Analysis	Patients receive SIM PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm I (SIM)	Quality-of-Life Assessment	Patients receive SIM PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm I (SIM)	Questionnaire Administration	Patients receive SIM PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm II (placebo)	Questionnaire Administration	ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm I (SIM)	Nutritional Intervention	Patients receive SIM PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm II (placebo)	Quality-of-Life Assessment	ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.
Arm II (placebo)	Placebo Administration	ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.

Primary Outcome Measures

Name	Time	Method
Post-operative Complications	Up to 30 days post surgery	A post-operative complication is defined as a binary indicator variable indicating whether the patient experienced any complication (any/none; Clavien-Dindo grades I-V). The primary analysis will be based on a multivariable logistic regression under intent-totreat among all randomized patients, irrespective of their eligibility status, adjusting for the specified stratification factors: a. Diversion type (neobladder versus \[vs.\] ileal conduit); b. Prior neoadjuvant chemotherapy (any vs. none); and c. Nutrition status (well nourished vs. moderate malnutrition). A Fisher's exact test will also be conducted to establish whether the results are sensitive to model assumptions. A single interim analysis for efficacy will be conducted when 50% of patients achieve their endpoint at the alpha=0.005 level. Accordingly, the final analysis will be conducted at the alpha=0.045 level. A separate analysis among all eligible randomized patients will also be conducted.

Secondary Outcome Measures

Name	Time	Method
Post-Op Complications	This outcome measure will be reported by 9/28/2025
Infections	This outcome measure will be reported by 9/28/2025
Skeletal Muscle Wasting	This outcome measure will be reported by 9/28/2025
High Grade Post-Op Complications	This outcome measure will be reported by 9/28/2025
Readmission Rates	This outcome measure will be reported by 9/28/2025
Quality of Life	This outcome measure will be reported by 9/28/2025
Disease Free Survival	This outcome measure will be reported by 9/28/2025

Trial Locations

Locations (46): Maine Medical Center-Bramhall Campus
🇺🇸
Portland, Maine, United States
Saint Joseph Mercy Brighton
🇺🇸
Brighton, Michigan, United States
IHA Hematology Oncology Consultants-Canton
🇺🇸
Canton, Michigan, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Genesys Hurley Cancer Institute
🇺🇸
Flint, Michigan, United States
Los Angeles County-USC Medical Center
🇺🇸
Los Angeles, California, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸
Westwood, Kansas, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Keck Medical Center of USC Pasadena
🇺🇸
Pasadena, California, United States
IHA Hematology Oncology Consultants-Brighton
🇺🇸
Brighton, Michigan, United States
University of Kansas Hospital-Indian Creek Campus
🇺🇸
Overland Park, Kansas, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
USC Norris Oncology/Hematology-Newport Beach
🇺🇸
Newport Beach, California, United States
Saint Joseph Mercy Chelsea
🇺🇸
Chelsea, Michigan, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸
Decatur, Illinois, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Lehigh Valley Hospital-Hazleton
🇺🇸
Hazleton, Pennsylvania, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
Saint Joseph Mercy Canton
🇺🇸
Canton, Michigan, United States
IHA Hematology Oncology Consultants-Chelsea
🇺🇸
Chelsea, Michigan, United States
Pocono Medical Center
🇺🇸
East Stroudsburg, Pennsylvania, United States
UTMB Cancer Center at Victory Lakes
🇺🇸
League City, Texas, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
🇺🇸
Grosse Pointe Woods, Michigan, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
Henry Ford West Bloomfield Hospital
🇺🇸
West Bloomfield, Michigan, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
University of Washington Medical Center - Montlake
🇺🇸
Seattle, Washington, United States
University of Kansas Clinical Research Center
🇺🇸
Fairway, Kansas, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
LSU Healthcare Network / Metairie Multi-Specialty Clinic
🇺🇸
Metairie, Louisiana, United States
Maine Medical Center- Scarborough Campus
🇺🇸
Scarborough, Maine, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Ascension Saint John Hospital
🇺🇸
Detroit, Michigan, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Huron Gastroenterology PC
🇺🇸
Ypsilanti, Michigan, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
IHA Hematology Oncology Consultants-Ann Arbor
🇺🇸
Ypsilanti, Michigan, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States