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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

Status
Active, not recruiting
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03757949
Enrollment
203
Registered
2018-11-29
Start date
2019-03-05
Completion date
2027-01-01
Last updated
2026-05-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bladder Carcinoma

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.

Interventions

OTHERLaboratory Biomarker Analysis

Correlative studies

DIETARY_SUPPLEMENTNutritional Intervention

Receive SIM PO

OTHERPlacebo Administration

Given PO

OTHERQuality-of-Life Assessment

Ancillary studies

OTHERQuestionnaire Administration

Ancillary studies

Sponsors

SWOG Cancer Research Network
Lead SponsorNETWORK
National Cancer Institute (NCI)
CollaboratorNIH

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Post-operative Complications (30 Days)Up to 30 days post surgeryA 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

MeasureTime frameDescription
Post-Op Complications (90 Days)Within 90 days after scheduled RCLate-phase post-operative complications within 90 days after scheduled RC
Infections30 days post-opNumber of post-operative infections
Skeletal Muscle Wasting30 days post op
High Grade Post-Op Complications30 days post-opHigh grade complications 30 days post-op, where high grade is Clavien-Dindo scores III-V
Readmission Rates30 days post-opCount of participants that were readmitted to hospital within 30 days post-op.
Quality of Life30 days post op
2-Year Disease Free Survival2 yearsDisease 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.

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORJill M Hamilton-Reeves

SWOG Cancer Research Network

Participant flow

Participants by arm

ArmCount
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. Laboratory Biomarker Analysis: Correlative studies Nutritional Intervention: Receive SIM PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
99
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. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
104
Total203

Baseline characteristics

CharacteristicArm II (Placebo)TotalArm I (SIM)
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
72 Participants138 Participants66 Participants
Age, Categorical
Between 18 and 65 years
32 Participants65 Participants33 Participants
Age, Continuous69.45 years68.8 years68 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
2 Participants6 Participants4 Participants
Race (NIH/OMB)
Black or African American
6 Participants10 Participants4 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Unknown or Not Reported
17 Participants39 Participants22 Participants
Race (NIH/OMB)
White
79 Participants147 Participants68 Participants
Region of Enrollment
United States
104 participants203 participants99 participants
Sex: Female, Male
Female
19 Participants41 Participants22 Participants
Sex: Female, Male
Male
85 Participants162 Participants77 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
9 / 9117 / 88
other
Total, other adverse events
68 / 9167 / 88
serious
Total, serious adverse events
2 / 912 / 88

Outcome results

Primary

Post-operative Complications

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.

Time frame: Up to 30 days post surgery

Population: Participants who are evaluable at day 30

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Arm I (SIM)Post-operative Complications56 Participants
Arm II (Placebo)Post-operative Complications51 Participants
Secondary

Disease Free Survival

Time frame: This outcome measure will be reported by 9/28/2025

Secondary

High Grade Post-Op Complications

Time frame: This outcome measure will be reported by 9/28/2025

Secondary

Infections

Time frame: This outcome measure will be reported by 9/28/2025

Secondary

Post-Op Complications

Time frame: This outcome measure will be reported by 9/28/2025

Secondary

Quality of Life

Time frame: This outcome measure will be reported by 9/28/2025

Secondary

Readmission Rates

Time frame: This outcome measure will be reported by 9/28/2025

Secondary

Skeletal Muscle Wasting

Time frame: This outcome measure will be reported by 9/28/2025

Source: ClinicalTrials.gov · Data processed: Jul 22, 2026