1. S1316 – The Malignant Bowel Obstruction Study A Prospective Comparative Effectiveness Trial for Malignant Bowel Obstruction
SWOG Study Chairs:
Robert S. Krouse, M.D., SAVAHCS/University of Arizona, Surgical Oncology
Brian Badgwell, M.D., MD Anderson Cancer Center
Nurse Chair:
Virginia Sun, R.N., Ph.D., City of Hope
Other Key Staff on S1316 are:
Biostatisticians: Garnet Anderson, Ph.D., and Katie Arnold, M.S., SWOG Statistical Center, Fred Hutchinson Cancer Research Center
Arizona Diet, Behavior and Quality of Life Assessment Lab
Cynthia A. Thomson, Ph.D., R.D.
Canyon Ranch Center for Prevention & Health Promotion
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

2. S1316 JACS Paper on MBO
Aggressive non-surgical palliative care options can help avoid an operation
There are many clinical scenarios when an operation is unlikely to benefit MBO patients
Can we test which treatment strategy (surgery vs. “aggressive” palliative management) is optimal in MBO?
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

3. S MBO Study Aims
To assess the quality of life outcome of the number of days alive and outside of the hospital within the first 91 days (13 weeks) after registration, for patients with malignant bowel obstruction who receive surgical intervention as compared to non-surgical intervention.
Research Questions:
Are there differences in HRQOL outcomes for patients with MBO who receive surgical intervention as compared to non-surgical intervention?
Are there clinical factors that predict better HRQOL outcomes for patients with MBO who receive surgical or non-surgical intervention?
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

4. S1316 – MBO Study Primary Endpoint
“Good days” = days out of the hospital and alive in the first 91 days (13 weeks) after registration
Secondary Endpoints
Days with NG tube
Days eating (Diet recalls)
HRQOL (MDASI-GI, EQ-5D-5L)
Morbidity/Mortality
Survival
The endpoints chosen were based on the extensive literature and clinical experience with MBO patients. The primary endpoint is “Days out of the hospital and alive”. There is ample evidence that the primary goal for patients with end stage disease is to be at home/out of the hospital. While it is imperative to collect other quality of life data, this is the optimal objective outcome for this population. Over 90% of hospice care is at home; therefore, days out of the hospital means days out of the acute care setting. While this is typically at home, it can also be at an inpatient hospice facility.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

5. S1316 - MBO Study Schema Surgery (50%) (Arm 1)
Meets all
eligibility
requirements (N=200)
Consents to randomization
(N=34)
Consents to non-randomized treatment
(N=166)
Surgery (50%) (Arm 1)
Non-surgical management (50%) (Arm 2)*
Surgery (Arm 3)
Non-surgical management (Arm 4)*
Primary Outcome: “Good days” = days out of the hospital and alive in the first 91 days (13 weeks) after registration
*Recommend a trial of somatostatin analog
Arms 1 and 3: Surgery
Patients on surgical management will undergo abdominal surgery as defined by the treating physician. Surgery is defined as an operative procedure. Information regarding patient treatment will be collected.
While randomization to Arm 1 will determine a patient’s initial care, the treating physician will take changes in their clinical course or other circumstances into account in determining the ongoing care plan.
Arms 2 and 4: Non-surgical Management
Patients on non-surgical management will be offered non-surgical management as determined by the treating physician. Information regarding patient treatment will be collected.
While the research team believes there is sufficient equipoise to randomize to such a trial, it is likely infeasible to accrue the entire population to a RCT at this time. Therefore, this study proposes to accrue a large number (n=180) and randomize a subset of these (n=50) accruing at selected institutions demonstrating substantial interest in and commitment to this question. This combined approach builds on the strengths of each design to give more reliable results. While the RCT component of this hybrid design could be considered a pilot trial, by embedding this trial in a larger non-randomized component, we believe we will have stronger inference than could be achieved by either alone.
All patients will be followed for 53 weeks.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

6. Data for primary endpoint reported
S1316 Patient Timeline
Follow-up Complete
Data for primary endpoint reported
Hospitalization with MBO
Day 0
Registration
Week 53
Week 13
Report all hospitalizations
Site calls patient weekly for assessments
Patient has dietary recall every 4 weeks
Site calls patient every 4 weeks for assessments
Patient has dietary recall every 4 weeks
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

7. S1316 - MBO Study Accrual Goal
Study will accrue 200 eligible patients
Study expects to accrue over 3 years
Two study components
Randomization component (n=34)
Non-randomized component (n=166)
While the research team believes there is sufficient equipoise to randomize to such a trial, it is likely infeasible to accrue the entire population to a RCT at this time. Therefore, this study proposes to accrue a large number (n=180) and randomize a subset of these (n=50) accruing at selected institutions demonstrating substantial interest in and commitment to this question. This combined approach builds on the strengths of each design to give more reliable results. While the RCT component of this hybrid design could be considered a pilot trial, by embedding this trial in a larger non-randomized component, we believe we will have stronger inference than could be achieved by either alone.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

8. S1316 – MBO Study Eligibility Criteria
MBO based on clinical/radiological criteria
MBO due to intra-abdominal cancer
Admission to hospital
Surgical candidate (would tolerate an operation and indication for surgery)
Equipoise – reasonable to treat operatively or non-operatively
Performance status (Zubrod Performance Status of one week prior to admission)
Able to complete questionnaires in English or Spanish
Required studies: H & P, CT or MRI for disease assessment, and serum albumin will be collected after admission but prior to treatment.
Optional studies: CBC and electrolyte panel will be collected after admission but prior to treatment.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

9. S1316 – MBO Study Ineligibility Criteria (cont’d)
MBO not due to intra-abdominal cancer
Patient actively dying
Patient requires an emergency surgical procedure, e.g., acute abdomen
Patient refuses to allow study staff to contact him/her for study follow-up
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

10. S1316 – MBO Study Timeline for Initial Patient Care
Up to 3 working days
Up to 2 working days
| | |
Seen by surgical team or completion of treatment for surgical eligibility
Register to S1316
Begin Treatment
Treatment may begin on the same day as the surgical consult as long as the order of events is preserved (registration, then treatment). Treatment must begin after registration. May have 48 hours of somatostatin-analogue.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

11. S1316 – MBO Study Initial Data Submission
Baseline data
Onstudy, MDASI-GI, EQ-5D-5L
MBO treatment and complications data for initial hospitalization
Pathology report to confirm primary cancer
Radiology reports to confirm MBO
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

12. S1316 – MBO Study Follow-Up
Weekly phone assessments and data collection by study site staff for first 13 weeks and every 4 weeks thereafter up to one year
Dietary recall phone calls every 4 weeks up to one year
MBO treatment and complications data for all hospitalizations in first 13 weeks
All patient-completed study forms will be administered via telephone or in person, if patient is in the hospital and allows an in-person visit. Follow-up assessments of patients are based from the date of registration. The time window for each phone assessment is +/- 2 days to allow for scheduling. If a follow-up call or visit is missed, the information that was missed will be included during the next completed call or visit.
Every effort should be made to collect the follow-up data in identical fashion across all study arms (surgical vs. non-surgical management, randomized vs. non-randomized).
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

13. S1316 – MBO Study Dietary Recall
Self-reported diet measurement methods
Relies on patient or caregiver to report foods consumed in prior 24-hour period
Collected by Arizona Diet, Behavior, Quality of Life Assessment Lab through phone contact
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

14. S1316 – MBO Study Criteria for Removal from Protocol Follow-up
Completion of 53 weeks on study
Medical condition that the treating investigator believes precludes continued participation
Patient refusal for any reason, including discontinuation of weekly phone calls
All reasons for discontinuation of follow-up will be documented but hospitalization data and vital status will still be reported.
If a patient no longer wants to complete the study phone calls, if appropriate, the site should ask if the follow-up calls can be made solely to the patient’s designated representative before removing a patient from follow-up.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

15. S1316 – MBO Study Analysis Plan
Study includes two components: randomized (n=34) and non-randomized (n=166)
Inference will be based on assigned treatment
Randomized component will use randomized treatment (intent to treat)
Non-randomized component will use initially chosen treatment (pseudo-intent to treat)
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

16. Analysis Plan (cont’d)
Initial analysis will use pooled data from both components
Use multivariate linear regression model
Include parameters for potential confounders
Include parameter for study component (randomized vs. non-randomized)
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

17. Analysis Plan (cont’d)
Assess bias in treatment group (surgical vs. non-surgical) between components (randomized vs. non-randomized)
No evidence of residual bias after controlling for potential confounders?
Use pooled data for primary analysis
Evidence of residual bias?
Report on both components
Use randomized data only for primary analysis
If the approach of Prentice et al., proves unwieldy because the number of covariates required to adjust for imbalance in the non-randomized component is too large for the sample size available, we will pursue the use of propensity scores.
A strategy similar to that used for the primary endpoint will be employed for secondary endpoints.
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

18. S1316 – MBO Study Recruitment Materials & Resources
Professional Slide Set
Patient Brochure
Resources:
S1316 webpage –
S1316 Working Group:
Conference calls
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015

19. Thank You
S MBO Professional Slide Set, Version 02 - Updated October 14, 2015