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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Bladder Carcinoma

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (SIM)<br>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<br>* Correlative studies<br>Dietary Supplement: Nutritional Intervention<br>* Receive SIM PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm II (placebo)<br>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<br>* Correlative studies<br>Other: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 30 days post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications | Complications will be defined using surgery-specific categories (ileus, deep vein thrombosis, pneumonia, wound infection, urinary tract infection, return to operation room, pulmonary embolus, myocardial infarction, cerebral vascular accident, dehiscence, sepsis, respiratory failure, bowel leak, urine leak, small bowel obstruction, death, or other). Post-operative ileus will be defined as a delay in feeding of greater than or equal to five days post operatively. | Up to 90 days post surgery | 
| Postoperative Infections | Infectious complications are defined by the need for intervention or prescription of non-prophylactic antibiotics to treat infection. In addition, infections will be categorized by intra-abdominal infection or surgical site infection. | Up to 90 days post surgery | 
| Anthropometrics and body composition | Changes in fat mass and non-bone lean tissue (muscle mass) will be assessed by dual-energy X-ray absorptiometry. The fat-free mass index and the appendicular skeletal muscle will be examined over time. Body weight (in a hospital gown without shoes) will be measured using a digital scale accurate to +/- 0.1 kg. Two measurements will be taken and averaged; if the two measurements differ by greater than 0.2 kg, a third measure will be taken. Height will be determined using a wall-mounted stadiometer (+/- 0.1 cm). Two measurements will be taken and averaged; if the two measurements differ by greater than 0.2 cm, a third measure will be taken. | Baseline to 30 days post surgery | 
| Quality of life | Functional Assessment of Anorexia/Cachexia Therapy will be completed. | Up to 30 days post surgery | 
| Readmission rates | Readmission will be defined as admission to any hospital after discharge home until 90 days after surgery. The reason for readmission will be recorded. | Up to 90 days post surgery | 
| Disease free survival | Will be explored using Kaplan Meier curves. | From date of randomization to date of first documentation of relapse/recurrence or death due to any cause, assessed up to 2 years | 
| Overall survival | Will be explored using Kaplan Meier curves. | From date of randomization to date of death due to any cause, assessed up to 2 years | 
| Performance status | Graded according to the Zubrod performance status scale. | Up to 3 years | 
| Infection rate | Will be determined by antibiotic use outside of prophylaxis. | At 30 and 90 days |