S 1316 The Malignant Bowel Obstruction Study A

S 1316 – 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 S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 - 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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-5 D-5 L) • Morbidity/Mortality • Survival S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 - MBO Study Schema Surgery (50%) (Arm 1) Consents to randomization (N=34) Meets all eligibility requirements (N=200) Non-surgical management (50%) (Arm 2)* Surgery (Arm 3) Consents to nonrandomized treatment (N=166) Primary Outcome: “Good days” = days out of the hospital and alive in the first 91 days (13 weeks) after registration Non-surgical management (Arm 4)* *Recommend a trial of somatostatin analog All patients will be followed for 53 weeks. S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 Patient Timeline Hospitalization with MBO Day 0 Registration • • • Data for primary endpoint reported Follow-up Complete Week 13 Week 53 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 - 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) S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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 0 - 2 one week prior to admission) • Able to complete questionnaires in English or Spanish S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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 S 1316 Begin 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – MBO Study Initial Data Submission • Baseline data – Onstudy, MDASI-GI, EQ-5 D-5 L • MBO treatment and complications data for initial hospitalization • Pathology report to confirm primary cancer • Radiology reports to confirm MBO S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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 S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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. S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – 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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

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 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

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 S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

S 1316 – MBO Study Recruitment Materials & Resources • Professional Slide Set • Patient Brochure Resources: • S 1316 webpage – https: //www. swog. org/swog -study-s 1316 -page • S 1316 Working Group: S 1316@swog. org • Conference calls S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015

Thank You S 1316 - MBO Professional Slide Set, Version 02 Updated October 14, 2015