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

A Randomized Phase III Double Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Bladder Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Placebo Administration; Dietary supplement: Nutritional Intervention

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.

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology/Hematology-Newport Beach
    • Pasadena, California, United States, 91105
      • Keck Medical Center of USC Pasadena
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Clinical Research Center
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Overland Park, Kansas, United States, 66211
      • University of Kansas Hospital-Indian Creek Campus
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center-Bramhall Campus
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center- Scarborough Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brighton, Michigan, United States, 48114
      • IHA Hematology Oncology Consultants-Brighton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton
    • Canton, Michigan, United States, 48188
      • IHA Hematology Oncology Consultants-Canton
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Chelsea, Michigan, United States, 48118
      • IHA Hematology Oncology Consultants-Chelsea
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
    • Ypsilanti, Michigan, United States, 48197
      • IHA Hematology Oncology Consultants-Ann Arbor
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Lehigh Valley Hospital-Hazleton
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • League City, Texas, United States, 77573
      • UTMB Cancer Center at Victory Lakes
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (SIM); Patients receive SIM PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Dietary supplement: Nutritional Intervention; Receive SIM PO
Placebo Comparator: Arm II (placebo); ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard of care surgery on day 0.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Placebo Administration; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Complications (30 Days)	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.	Up to 30 days post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Op Complications (90 Days)	Late-phase post-operative complications within 90 days after scheduled RC	Within 90 days after scheduled RC
Infections	Number of post-operative infections	30 days post-op
Skeletal Muscle Wasting		30 days post op
High Grade Post-Op Complications	High grade complications 30 days post-op, where high grade is Clavien-Dindo scores III-V	30 days post-op
Readmission Rates	Count of participants that were readmitted to hospital within 30 days post-op.	30 days post-op
Quality of Life		30 days post op
2-Year Disease Free Survival	Disease free survival is defined as time from surgery to documented recurrence or death from any cause. The number reported is the number of participants who survived two years without documented recurrence.	2 years

Collaborators and Investigators

• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jill M Hamilton-Reeves, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Actual): January 1, 2024
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 1, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: S1600 (Other Identifier: CTEP); UG1CA189974 (U.S. NIH Grant/Contract); NCI-2017-02442 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SWOG-S1600 (Other Identifier: DCP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No