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

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03757949
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 200
• Locations: 47
• Arms: 2
• Anticipated Duration (Months): 86.3
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Carcinoma	Other: Laboratory Biomarker Analysis; Dietary Supplement: Nutritional Intervention; Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration	Phase 3

Detailed Description

PRIMARY OBJECTIVE:

1. 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:

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

2. 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.

3. 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:

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

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

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

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

TRANSLATIONAL MEDICINE OBJECTIVES:

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

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

3. 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Phase III Double Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes
• Actual Study Start Date: Feb 21, 2019
• Anticipated Primary Completion Date: Jul 1, 2023
• Anticipated Study Completion Date: May 1, 2026

Arms and Interventions

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; Dietary Supplement: Nutritional Intervention; Receive SIM PO; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies
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: Placebo Administration; Given PO; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. 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

1. Complications [Up to 90 days post surgery]

   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.

2. Postoperative Infections [Up to 90 days post surgery]

   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.

3. Anthropometrics and body composition [Baseline to 30 days post surgery]

   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.

4. Quality of life [Up to 30 days post surgery]

   Functional Assessment of Anorexia/Cachexia Therapy will be completed.

5. Readmission rates [Up to 90 days post surgery]

   Readmission will be defined as admission to any hospital after discharge home until 90 days after surgery. The reason for readmission will be recorded.

6. Disease free survival [From date of randomization to date of first documentation of relapse/recurrence or death due to any cause, assessed up to 2 years]

   Will be explored using Kaplan Meier curves.

7. Overall survival [From date of randomization to date of death due to any cause, assessed up to 2 years]

   Will be explored using Kaplan Meier curves.

8. Performance status [Up to 3 years]

   Graded according to the Zubrod performance status scale.

9. Infection rate [At 30 and 90 days]

   Will be determined by antibiotic use outside of prophylaxis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
3	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California	United States	92663
5	Keck Medical Center of USC Pasadena	Pasadena	California	United States	91105
6	University of Colorado Hospital	Aurora	Colorado	United States	80045
7	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
8	Northwestern University	Chicago	Illinois	United States	60611
9	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
10	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
11	University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
12	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
13	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas	United States	66211
14	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
15	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana	United States	70006
16	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
17	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
18	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
19	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan	United States	48114
20	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
21	IHA Hematology Oncology Consultants-Canton	Canton	Michigan	United States	48188
22	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
23	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan	United States	48118
24	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
25	Henry Ford Hospital	Detroit	Michigan	United States	48202
26	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
27	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
28	Hurley Medical Center	Flint	Michigan	United States	48503
29	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan	United States	48236
30	Sparrow Hospital	Lansing	Michigan	United States	48912
31	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
32	Huron Gastroenterology PC	Ypsilanti	Michigan	United States	48106
33	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan	United States	48197
34	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
35	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
36	University of Rochester	Rochester	New York	United States	14642
37	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
38	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
39	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
40	Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
41	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania	United States	18201
42	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
43	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
44	UTMB Cancer Center at Victory Lakes	League City	Texas	United States	77573
45	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
46	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
47	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jill M Hamilton-Reeves, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT03757949
• Other Study ID Numbers: S1600; NCI-2017-02442; S1600; SWOG-S1600; S1600; UG1CA189974
• First Posted: Nov 29, 2018
• Last Update Posted: Mar 16, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Urinary Bladder Neoplasms

Study Results

No Results Posted as of Mar 16, 2022