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TITLE: Giving Information Strategically and Transparently in Solid Tumor Cancer NCT \# (Phase 1): NCT04158908 NCT \# (Phase 2): NCT04179305 IRB **Protocol** \#: 19-07020392 Version **Date:** April 25th, 2022 Funding **Source(s):** National Institutes of Health, National Cancer Institute, Weill Cornell Medical College  
PrincipalInvestigator: Holly G Prigerson, PhD  
420 E 70th St., 3rd Floor, Suite B  
(646) 962-2882  
(646) 962-0812  
hgp2001@med.cornell.edu  
| Paul K. Maciejewski, PhD 420 E 70th St., 3rd Floor, Suite B (646) 962-7169 (646) 962-0812 pam2056@med.cornell.edu   |
|---------------------------------------------------------------------------------------------------------------------|  
| Ashish Saxena, MD, PhD 420 E 70th St ., 3Rd Floor (646) 962-2066 (646) 962-1603 ahs9018@med.cornell.edu   |
|-----------------------------------------------------------------------------------------------------------|  
| Sophia Kakarala 420 E 70th St., 3rd Floor, Suite B (646) 962-5637 sok4004@med.cornell.edu   |
|---------------------------------------------------------------------------------------------|  
Co-Investigators:
MedicalMonitor:
N/A
ParticipatingSites: N/A  
| Heather Derry, PhD 420 E 70th St., 3rd Floor, Suite B (646) 962-7149 (646) 962-0812 hmd2002@med.cornell.edu Manish A. Shah, MD 1305 York Ave., 12th Floor (646) 962-6200 (646) 962-1607 mas9313@med.cornell.edu Andrew Epstein, MD 1275 York Ave. (646) 888-4313 epsteina@msckcc.org ane9006@med.cornell.edu   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| Table of Contents                                                                                                                                      |                          |
|--------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------|
| LIST OF ABBREVIATIONS                                                                                                                                  |                          |
| 1. PROTOCOL SUMMARY                                                                                                                                    |                          |
| 1.1 Study Objectives .                                                                                                                                 |                          |
| 1.1.1 Objectives                                                                                                                                       | 3                        |
| 1.1.2 Hypotheses / Research Questions                                                                                                                  | 3                        |
| 2. BACKGROUND AND SIGNIFICANCE .                                                                                                                       |                          |
| 3. STUDY DESIGN AND METHODS                                                                                                                            |                          |
| 3.1 Overall Design                                                                                                                                     |                          |
| 3.2 Interviews, Focus Groups, Surveys, and/or Observations                                                                                             |                          |
| 4.1 Study Population .                                                                                                                                 |                          |
| 4.2 Inclusion Criteria                                                                                                                                 |                          |
| 4.3 Exclusion Criteria .                                                                                                                               |                          |
| 4.4 Strategies for Recruitment and Retention .                                                                                                         |                          |
| 5. REGISTRATION PROCEDURES .                                                                                                                           |                          |
| 5.1 Subject Registration (WCM only) .................................................................................................................9 |                          |
| 5.2 Subject Registration (Sub-sites) .                                                                                                                 |                          |
| 6. STUDY PROCEDURES                                                                                                                                    |                          |
| 6.1 Schedule of Assessments                                                                                                                            |                          |
| 7.1 DATA REPORTING / REGULATORY CONSIDERATIONS .                                                                                                       |                          |
| 7.2 Data Collection                                                                                                                                    |                          |
| 7.2.1 REDCap                                                                                                                                           | 11                       |
| 7.3 Regulatory Considerations                                                                                                                          |                          |
| 7.3.1  Institutional Review Board/Ethics Committee Approval                                                                                            | 11                       |
| 7.3.2  Ethical Conduct of the Study                                                                                                                    | 12                       |
| 7.3.3 Informed Consent                                                                                                                                 | 12                       |
| 7.3.4 Compliance with Trial Registration and Results Posting Requirements                                                                              | 12                       |
| 7.3.5 Record Retention                                                                                                                                 | 12                       |
| 8. STATISTICAL CONSIDERATIONS                                                                                                                          |                          |
| 8.1                                                                                                                                                    | Sample Size/Accrual Rate |
| 8.2 Stratification Factors .                                                                                                                           |                          |
| 8.3 Analysis of Endpoints                                                                                                                              |                          |
| 8.3.1 Analysis of Primary Endpoints                                                                                                                    | 13                       |
| 9.1  Adverse Event Definition                                                                                                                          |                          |
| 9.1.1  Adverse Event Characteristics and Related Attributions                                                                                          | 14                       |
| 9.1.2 Recording of Adverse Events                                                                                                                      | 14                       |  
9.1.3 Reporting of AE to WCM IRB 14 9.1.4 Reporting Eventsto **Participants** 14 9.1.5 Events of Special **Interest** 14 9.1.6 Reporting of **Pregnancy** 15 10. UNANTICIPATED PROBLEMS INVOLVING RISKS TO SUBJECTS OR *OTHERS*............................... 15 10.1 Definition of Unanticipated ProblemsInvolving Risksto Subjects or **Others(UPIRTSO)**15 10.1.1Unanticipated Problem **Reporting** 15 11. SAFETY STOPPING RULES………………………………………………………………………………………………………15 REFERENCES............................................................................................................................................... 15
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confidentialitystatement

This document is confidential and isto be distributed for review only to investigators, potential investigators, consultants,study staff, and applicable independent ethics committees orinstitutional review boards. The contents of this documentshall not be disclosed to others without written authorization from WCM.
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list of abbreviations

| ACP    | Advanced Care Planning                                      |
|--------|-------------------------------------------------------------|
| AE     | Adverse Event                                               |
| CFR    | Code of Federal Regulations                                 |
| CwC    | Coping with Cancer                                          |
| CRF    | Case Report Form                                            |
| CTSC   | Clinical Translational Science Center                       |
| DSMC   | Data Safety Monitoring Committee                            |
| DSMP   | Data Safety Monitoring Plan                                 |
| EoL    | End of Life                                                 |
| FDA    | Food andDrug Administration                                 |
| GCP    | Good Clinical Practice                                      |
| GIST   | Giving Information Strategically and Transparently          |
| HIPAA  | Health Insurance Portability and Accountability Act of 1996 |
| HRBFA  | Human Research Billing Analysis Form                        |
| HUD    | Humanitarian Use Device                                     |
| ICF    | Informed Consent Form                                       |
| IDE    | InvestigationalDevice Exemption                             |
| IND    | InvestigationalNew Drug                                     |
| IRB    | Institutional Review Board                                  |
| PHI    | ProtectedHealth Information                                 |
| PI     | Principal Investigator                                      |
| REDCap | Research ElectronicData Capture                             |
| SAE    | Serious Adverse Event                                       |
| SUSAR  | SuspectedUnexpected Serious Adverse Reaction                |
| UIRTSO | Unanticipated Problem Involving Risksto Subjects or Others  |
| WCM    | Weill Cornell Medicine                                      |  
| 1. Protocol Summary Full Title:   | Giving Information Systematically and Transparently in Solid Tumor Cancer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      |
|-----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Short Title:                      | Oncolo-GIST                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |
| PrincipalInvestigator:            | Holly G. Prigerson, PhD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        |
| StudyDescription:                 | The study will develop,refine and pilot test the Oncolo-GIST clinician training intervention. The training is aimed at enhancing the clinician's communication with patients by teaching to relay information both sensitively and in simple terminology.                                                                                                                                                                                                                                                                                                                                                                                                                      |
| Sample Size:                      | Phase 1 Interviews: N=20 (N=10 clinicians, N=10 bereaved caregivers) Phase 2: N= 54 (N=50 patientsubjects, N=4 clinician subjects)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| Enrollment:                       | This study will enroll 74 subjects and screen up to 250 subjects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |
| Study Population:                 | Phase 1 Interviews: Bereaved Caregiversubjects will be caregivers of patients who died in the past year with a primary diagnoses of GI or lung cancers. Clinician subjects will be either oncologists, palliative care physicians, nurses, nurse practitioners,social workers and psychologists who care for patients with metastatic GI and lung cancers. Phase 2: Patientsubjects will be adults(18+) diagnosed with lung, head and neck, or GI cancer, with a progression of their disease after one line of therapy. Clinician subjects will be Lung, Head and Neck, or GI oncologists. All subjects' primary language will be English and will have full mental capacity. |
| EnrollmentPeriod:                 | Phase 1 (Interviews): 12 months Phase 2: 19 Months                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| Study Design:                     | Phase 1 (Interviews): Interventionmanual development Phase 2: Intervention phase (two-group pilot randomized trial).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |
| Participants:                     | Participants will be recruited at Weill Cornell Medical College/ New-York Presbyterian Hospital, at the Lung and GI Cancer centers.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            |
| StudyDuration:                    | 31months Start date: Jan 22, 2020 End date: July 25, 2022 (end enrollment); January 25th, 2023 (end data analysis and all other activities)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |
| ParticipantDuration:              | Phase 1 Interviews: 2 hours Phase 2: 4 months(with patientstatus monitoring up to 12 months)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |
| PrimaryObjective:                 | To assessthe effectiveness of the Oncologist intervention by examining the patient's degree of prognostic understanding after discussing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       |  
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| SecondaryObjectives:   | To examine the effects on patients of having better prognostic understating, including its effect on their quality of life, the type of care they choose to receive and whether or not the care they received was consistent with the patient's preferences and values.                                                                                                                                                                                                                                                                                                                                                                                                                          |
|------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Endpoints:             | Outcome will be a training manual for cliniciansthat teaches the Oncolo-GIST methods of communication. The efficacy of the intervention will be determined by measuring the patient's prognostic understanding using our validated 4-item assessment. The assessment will determine if the patient understood the scan results as well as the expected outcomes oftreatments offered. Outcomes will also include whether a DNR order was completed for the patient, the patients quality of life (McGill Quality of Life measure) , patient performance status(e.g., Eastern Cooperative Oncology Group, ECOG), as well asthe type care received (e.g., anticancer, intensive, palliative care). |
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1.1 studyobjectives 1.1.1 objectives

Objective 1: To develop and refine Oncolo-GIST, an intervention aimed at enhancing clinicians' communication with patients by teaching to relay information both sensitively and in simple terminology, by receiving feedback from clinicians as well from bereaved family members of cancer patients.  
Objective 2: To determine feasibility and acceptability of Oncolo-GIST in a cluster trial in 50 patients with advanced cancer and 4 clinicians.  
Objective 3: To test the preliminary efficacy of Oncologist on the 1) patients prognostic understanding 2) Other aspects of patient care including type of care, quality of life, and "value consistent" care.
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1.1.2 hypotheses / researchquestions

Hypothesis 1: The Oncolo-GIST intervention will be demonstrated to be feasible and acceptable to both clinicians and patients. Hypothesis 2: The Oncolo-GIST intervention will be associated with advanced cancer patients' understanding of theirscan results and prognosis(i.e., that they likely have months, not years, left to live).
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2. backgroundand significance

Informed consent requires an individual to have a clear understanding of the facts, implications, and consequences of an action.  
1 2 3 Bioethical principles, rooted in a respect for human dignity, necessitate that patients have a basic understanding of their illness and the risks and benefits of treatments proffered. Patients cannot make informed decisions about their care in the absence of knowledge of their prognosis or expected outcomes of treatments under consideration. It is alarming how unaware of their prognosisthe vast majority of patientsin our NCI-funded Coping with Cancer(CwC) R01s proved to be. Among CwC advanced cancer patients with a median survival of 5 monthsfrom our baseline assessment, we found only 5% accurately understood that they had incurable cancer, were terminally ill, were at a late- or end-stage of their illness, and likely had months, but not years, left to live.  
4 These findings highlight the ethical imperative of ensuring that patients have sufficient understanding of their prognosis, and expected risks/benefits of treatments being offered to them, for making informed choices. Preliminary evidence from CwC hasshown that patients who get the gist that death is near are more likely to: a) engage in advance care planning (ACP) 5 6 b) receive less burdensome, intensive, and unbeneficial EoL care (e.g., fewer ICU stays, inappropriate palliative chemotherapy),
5 6 7 8 and c) more value-consistent EoL care.  
6 Although we found that 71% of these patientsstate that they would want their oncologist to tell them their prognosis, only 17.6% stated that their oncologist had discussed their prognosis(i.e., life-expectancy) with them.  
9 We find that patient prognostic understanding is improved by oncologist discussions of prognosis, 4 10 7 but that the manner of communication mattersfor patients to "get the gist" that death is near.  
10
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approach has enormous potential to address each of these needs. By enabling more patientsto make informed medical choices,the Oncolo-GIST approach is expected to uphold bioethical principles by promoting patients' capacity to engage in truly informed medical decision-making which, based on prior findings, is also expected to result in better EoL outcomes(e.g., less intensive, more palliative and more value-consistent EoL care). 3 7 11
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3. study design and methods

The overall goals are to refine and demonstrate the feasibility of implementing the Oncolo-GIST intervention, determine its acceptability to oncologists, and potential for improving advanced cancer patients' prognostic understanding. In pursuing these goals, thisstudyaimsto determine the promise of the Oncolo-GIST approach for affecting the targeted outcomes and given positive results, to position us for a larger RCT. We, thus, propose to examine key aspects of intervention development,to evaluate the NIH's Stage I activities of the Stage Model of Behavioral Therapies(e.g.,
intervention refinement, adaptation, and pilot testing),12 13 and to exploreOncolo-GIST's preliminary efficacy.  
Both qualitative and quantitative methods will be used in Phase 1. During the Phase 1 interviews
(Aim \#1) we will obtain feedback from relevantstakeholders/key informants(bereaved caregivers and clinicians) on an early draft of the Oncolo-GIST manual and proposed approach using a version of the Delphi method 14 in which we interview bereaved family caregivers of advanced cancer patients(n=10) and oncology clinicians who care for patients with advanced gastrointestinal (GI) and thoracic (lung) cancers(n=10). The participants will have the option of completing a recorded phone interview or answering identical questions via a link to REDCap. Participants will also be asked demographic and oncology based communication questionsspecific to either clinicians or caregivers.  
In Phase 2, for the pilot cluster RCT study (Aim \#3), we will recruit adult patients(n=50) with metastatic GI, head and neck, or lung cancers with scan resultsthat reveal progression (worsened disease) on an initialsystemic treatment; that is, patients whose life-expectancy can reliably be estimated to be months, not years. 5 9 Medical oncologists(n=4) who care for these patients will also be consented forstudy participation and half (n=2) will be randomized to receive the brief "OncoloGIST communication" training. The Oncolo-GIST training will provide instruction in how to introduce the topic of prognosis, describe scan results as "worse," prognosis as "likely months, not years," and expected treatment outcomes(e.g., "not expected to be cured by treatment," and expected impact on quality of life - that is, whether the anticancer treatment is likely to make them feel overall better or worse). We expect 12-13 patients will be clustered within each of the 4 oncologists. Hierarchical Linear Modeling (HLM) techniques will be employed to addressthe non-independence of patient assessments within each cluster. Patients(n=25) will be seen by either an Oncolo-GIST
trained oncologist or an oncologist not trained in the intervention; that is, usual care (n=25).  
Patientsin both arms will have met the same eligibility criteria (i.e., have similar prognoses).  
Thus, we will get initial feedback on the Oncolo-GIST intervention from relevant stakeholders and key informants, obtain information on the patient and oncologist experience with the intervention and evaluate itsfeasibility and acceptability. Finally, we will obtain preliminary effectsize estimates
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2022 on the Oncolo-GIST Version 2.0's effect on our primary outcome - patient prognostic understanding
- to inform the planning of a future largerscale efficacy randomized controlled trial (RCT). Patients will be assessed by trained research staff in the week prior to a scheduled meeting with their oncologist to discussthe scan results. This will provide patients' baseline levels of prognostic understanding and enable us to determine how the intervention relatesto pre-postscan visit changesin prognostic understanding. Although the first scheduled scan afterstudy enrollment may not reveal progressive disease, we have been assured by Drs. Epstein and Saxena that only exceptional cancer patients will not progress within 12 months of baseline. We thus propose to follow patientsfor 12 months or until a progression is detected in the scan, whichever comes first.  
Patients will be assessed pre-scan, post-scan within a week of that progressive scan visit and after their two next scans, if applicable. [see Human Subjects section for Study Timeline & Assessment Schedule and details of assessment procedures]. Although not all patients are expected to die within the study observation period, given a median life expectancy of ~4-5 monthsfrom baseline, 9 we expect nearly half of the enrolled patients will die 4 months from baseline, and that the vast majority will die during the study observation period. Thus, for all patients enrolled in this study, the medical care that they receive can reasonably be considered end-of-life care, whether they die during the study observation period or not. Informed consent of participants will occur in-person or will be conducted remotely by sending the participantsthe consent form by mail orsecure file transfer(transfer.weill.cornell.edu) or via a REDCap Informed Consent form (see attached) The REDCap form will be implemented in the following manner to ensure informed consent: a research assistant will send the form to a participant prior to a scheduled phone call, go through the consent with the participant overthe phone, and answer any questions. The participant will need to type the correct name of the person who recruited them in the REDCap form: a wrong answer will be counted as "not consented." REDCap has been automatically set up with the e-consent framework to auto-archive consents and email a PDF copy of the signed form to the participant. A research assistant will then call the participants to go over consent and answer any questionsthey may have priorto any assessments.  
Participants will keep one copy of the consent form and send one copy back by mail orsecure file transfer priorto any assessments/data collection.  
Phase 2 documents will be submitted upon completion of the Phase 1 Interviews and the *Phase* 1 Open Trial respectively. No participants will be enrolled without IRB approval of these *documents.*
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3.2 interviews focusgroups surveys and/orobservations

Phase 1 Interviews: Clinicians and bereaved caregivers will complete a one-time, 2 hour phone study session or REDCap survey (including embedded intervention manual) link.  
Phase 2: Patients will be assessed in the week prior to theirscheduled scan, within 1 week of the clinic visit in which progressive scan results are discussed, and then after their next two scans, if they have them, to explore intervention effects on primary and secondary outcomes,respectively. Oncologists will be assessed in the week following thatsame clinic visit to obtain their impressions of the discussion of prognosis and the patient's prognostic understanding. All these assessments will take 20-30minutes.  
Trained oncologists will complete a brief (5-minute) post-training quiz, and all oncologists will complete a brief (5-minute)survey on Oncolo-GIST at the end of the study. Additionally, patients will be monitored via EPIC for progression of disease up to 12 months.  
*Location* Phase 1 interviews of caregivers and clinicians will take place at a location convenient to the participant over the phone or via REDCap. Assessments of patients and cliniciansin the pilot stage will take place in-person in clinic, at a time convenient for the participant at a different appointment, or overthe telephone. Patients in Phase 2 will also have the option of completing the surveysthemselves via a secure web link if this is more convenientto them.  
Person *Identifiers* Co-investigators may review EPIC to identify potential participants who meet eligibility.  
Contact information and appointment information will also be collected for eitherinperson or letter(postal and email) recruitment. Only data from potential participants will be stored on secure servers. Patientsubjects will also have data collected via medical chart abstraction including diagnoses, medications, advanced directives, and types of care received (e.g. hospice). These data will be deleted upon completion of the study.
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b. study instruments

Phase 1 Interviewsfor both clinician and bereaved caregiversubjects will consist of a survey including demographics and oncology based communication questions specific to eitherthe clinicians or caregivers. After each section of the Oncolo-GIST
manual, participants will answer open-ended questions about the module they just reviewed.  
Phase 2 patients will be screened with a mentalstatus questionnaire and health literacy assessment. At the first visit they will answer an assessment battery including but not limited to questions about treatment and mentalstatus prior to discussing theirscan results. After the scan results, patients will answer questionsto assess prognostic understanding and treatment preferences at 3 post-scan time points(1 week after initialscan, one week aftersecond scan, one week afterthird scan from enrollment)). Trained co-investigators will also collect data via medical chart abstraction. Clinicians(Phase 2) will answer an initial demographic survey and surveysincluding prognosis questions, patient understanding, and patient medical statusfor each patient participant. Clinicianstrained in Oncolo-GIST will also complete a short post-training quizto assesstheir understanding of the Oncolo-GIST
manual. All clinicians will complete a briefstudy completion questionnaire to assess the feasibility and acceptability of the Oncolo-GIST method.
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referral information

Data collected/received from participants will be reviewed within 24-48 hours and research study staff will be responsible for addressing elevated psychological symptoms/suicidality identified on the assessmentsso that timely and appropriate psychiatric assessment and care can be provided. If a participant at acute risk of self-harm or harm to others cannot be reached by the study team within 3 hours
(after at least two phone call attempts and an email requesting a call back), the participant's emergency contact(s) will be contacted.
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4. studydesign 4.1 study population

Phase 1 Interviews: Bereaved Caregiversubjects will be caregivers of patients who died in the past year with a primary diagnoses of GI or lung cancers. Clinician subjects will be oncologists, palliative care physicians, nurses, nurse practitioners,social workers, or psychologists who care for patients with metastatic GI and lung cancers.  
Phase 2: Patientsubjects will be adults(18+) diagnosed with lung or GI cancer, with a progression of their disease after one line of therapy. Clinician subjects will be Lung, Head and Neck, or GI oncologists. Allsubjects' primary language will be English and will have full mental capacity.
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4.2 inclusioncriteria

Phase 1 Interviews:
BereavedCaregivers:
1. Caregivers of patients who died in the past year with a primary diagnoses of GI or lung cancer 2. Fluent in English Clinicians:
1. Currently care for patients with metastatic GI and lung cancers as an oncologist, palliative care physician, nurse, nurse practitioner,social worker, or psychologist
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phase 2 patients

1. Male or female ≥ 18 years of age.  
2. Receiving ongoing care (≥ 2 visits) that includesregularscans 3. Progression on at least 1 line ofsystemic cancer therapy 4. Prognosisfrom an oncologist of lessthan 12 months 5. Receiving care from an oncologist participating in the Oncolo-GIST study 6. Fluent in English Clinicians:
1. Specialize in Lung, Head and Neck, and GI cancers 2. Currently provide care at the WCM Lung, Head and Neck, and GI cancer clinics 3. Fluent in English
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4.3 exclusioncriteria

Phase 1 Interviews:
BereavedCaregivers:
1. Caregivers of patients who died longer than 1 yearfrom the time of enrollment 2. Caregivers of a patient that did not have a primary diagnoses of GI or lung cancer 3. Not fluent in English Clinicians:
1. Does not currently care for patients with metastatic GI and lung cancers as either an oncologist, palliative care physician, nurse, nurse practitioner,social worker, or psychologist Phase 2:
Patients:
1. Under 18 years of age 2. Not receiving ongoing cancer care (≥ 2 visits) that includes regularscans 3. Not progressing on at least 1 line ofsystemic cancer therapy 1. Prognosisfrom an oncologists of 12 months or more 4. Not receiving care from an oncologist participating in the Oncolo-GIST study 5. Not fluent in English 6. Cognitive impairment, as indicated by a score of <8 on the Short Portable Mental Status Questionnaire or a diagnosis of dementia or a related condition Clinicians:
1. Does notspecialize in Lung, Head and Neck, and GI cancers 2. Does not currently provide care at the WCM Lung, Head and Neck, and GI cancer clinics 3. Not fluent in English
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4.4 strategiesfor recruitment and retention

Phase 1 Interviews: Clinicians and bereaved caregivers will be recruited by targeted sampling. We will use WCM's EPIC system as well request referrals from Weill Cornell Medicine (WCM) clinicians to recruit 10 bereaved caregivers of GI and lung cancer patients who died within the past year.  
Trained research co-investigators willscreen deceased patients using EPIC after referral. If deemed eligible, caregivers will be contacted by either phone or email by non-clinician co-investigators. Oncology cliniciansincluding oncologists, palliative care physicians, nurses, nurse practitioners,social workers, and psychologists who care for patients with GI and lung cancer, will be identified for recruitment via convenience and snowballsampling by either phone or email. These clinicians are known by co-investigators and/ortheir affiliates. Recruitment emails will include an attached flyer.  
Flyers will also be distributed on WCM/NYP properties. Phone recruitment will be by script and will include information from the flyer. Participants will not be contacted more than twice if there is no response and if at any point, a potential participant asks not to be contacted,study staff members will thank them for their time, and be put on a do not contact list. Participants will receive $100 compensation via a ClinCard afterthe interview is completed.  
Phase 2: Patients will be identified from weekly reviews of patient charts and discussions with the WCM GI, Head and Neck, and lung clinic staff working alongside Dr. Manish Shah and Dr. Ashish Saxena, respectively. Trained research assistants(RA) willscreen patients at the Lung and GI Clinics for eligibility, using WCM's EPIC system. If deemed eligible (see eligibility and exclusion criteria), the research assistant will approach the patient in clinic, to explain the study, and the study procedures.  
Flyers will also be distributed on WCM/NYP properties. Patientsubjects will receive $25 compensation via ClinCard after each interview is completed, with a possible total of $100 by the end of the study.  
- Anticipated *accrualrate* o Phase 1 Interviews Recruit and enroll 10 oncology clinicians and 10 bereaved in the 1st 6 months of the study o Phase 2 Recruit and enroll 50 patients(3/month for ~ 18 months)
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5. registrationprocedures

5.1 Subject Registration (WCM **only)**
Subjects will be registered within the WRG-CT as per the standard operating procedure for SubjectRegistration.  
5.2 Subject **Registration(Sub-sites)**
Not Applicable
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6. study procedures

6.1 Schedule of **Assessments**  
| Pre-study                              | Visit 1   |
|----------------------------------------|-----------|
| (Interview)                            |           |
| Screening                              | X         |
| Informed Consent (see note)            | X         |
| Review of Oncolo-GIST intervention     | X         |
| Demographics                           | X         |
| Oncology Based Communication Questions | X         |
| Semi-structuredInterview               | X         |  
Table 1. Schedule of trial eventsfor Phase 1 Interviews(Bereaved Caregivers and Clinicians)
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2022 Table 2. Schedule of trial eventsfor Phase 2  
| Post-Scan 2                                                                      | Post-Scan 3   | Post-Scan 4 (up to 12 months)   |             |    |    |
|----------------------------------------------------------------------------------|---------------|---------------------------------|-------------|----|----|
| Short Portable Mental Status QuestionnaireS                                      | P             | X                               |             |    |    |
| Health Literacy Assessment (REALM)S                                              | P             | X                               |             |    |    |
| InformedConsent                                                                  | B             | X                               | Post-Scan 1 |    |    |
| PreStudy                                                                                  | PreScan               | (approx. 1                      |             |    |    |
| Arm                                                                              | week)         |                                 |             |    |    |
| Oncolo-GIST Training (Clinicians)                                                | C*            | X                               |             |    |    |
| Demographics                                                                     | P             | X                               |             |    |    |
| 4 Item Illness Understanding                                                     | P             | X                               |             |    |    |
| TreatmentIntent                                                                  | P             | X                               |             |    |    |
| TreatmentPreferences                                                             | P             | X                               |             |    |    |
| CWC II Psychological questions                                                   | P             | X                               |             |    |    |
| NCCNDistress Thermometer                                                         | P             | X                               |             |    |    |
| The Human Connection Scale                                                       | P             | X                               | X           | X  | X  |
| HADS                                                                             | P             | X                               | X           | X  | X  |
| McGill Quality of Life Questionnaire                                             | P             | X                               | X           | X  | X  |
| PSWQ-Ultra Brief                                                                 | P             | X                               |             |    |    |
| PANAS                                                                            | P             | X                               |             |    |    |
| Primary Appraisal Secondary Appraisal (PASA) items(Threat and                    | P             | X                               |             |    |    |
| Challenge subscales only) Post Scan Clinician Questionnaire                      | C             | X                               |             |    |    |
| Medical Chart Abstraction                                                        | C             | X                               | X           | X  |    |
| Post Scan PatientQuestionnaire                                                   | P             | X                               | X           | X  |    |
| TrainingQuiz                                                                     | C*            | X                               |             |    |    |
| Post-StudyQuestionnaire                                                          | C             | X                               |             |    |    |
| C = Clinicians, P = Patients, B = Both, S = Screening, * = Intervention Arm Only |               |                                 |             |    |    |  
Note: The Post-Scan 4 Chart Abstraction will occur when monitoring if progression of the disease is *found* after Post-Scan 3 or the patient is deceased; up to 12 months.  
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Version Date: April 25th, 2022
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7.1 data reporting / regulatory

The data collection plan for this study isto utilize REDCap to capture all treatment, toxicity, efficacy, and adverse event data for all enrolled subjects.  
7.2.1 **REDCap**
REDCap (Research Electronic Data Capture) is a free data managementsoftware system that is fully supported by the Weill-Cornell Medical Center CTSC. It is a tool for the creation of customized,secure data managementsystemsthatinclude Web-based data-entry forms, reporting tools, and a full array ofsecurity featuresincluding user and group based privileges, authentication using institution LDAP system, with a full audit trail of data manipulation and export procedures. REDCap is maintained on CTSC-owned serversthat are backed up nightly and support encrypted (SSL-based) connections. Nationally, the software is developed, enhanced and supported through a multi-institutional consortium led by the Vanderbilt University CTSA.
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7.3 regulatoryconsiderations 7.3.1 institutional reviewboard/ethics

As required by local regulations, the Investigator will ensure all legal aspects are covered, and approval of the appropriate regulatory bodies obtained, before study initiation.  
Before initiation of the study at each study center, the protocol, the ICF, other written material given to the patients, and any other relevant study documentation will be submitted to the appropriate Ethics Committee. Written approval of the study and all relevant study information must be obtained before the study center can be initiated or the IP is released to the Investigator. Any necessary extensions or renewals of IEC/IRB approval must be obtained for changes to the study, such as amendments to the protocol, the ICF, or other study documentation. The written approval of the IEC/IRB together with the approved ICF must be filed in the study files.  
The Investigator will report promptly to the IEC/IRB any new information that may adversely affect the safety of the subjects or the conduct of the study. The Investigator will submit written summaries of the study status to the IEC/IRB as required. On completion of the study, the IEC/IRB will be notified that the study has ended.  
All agreed protocol amendments will be clearly recorded on a protocol amendment form and will be signed and dated by the original protocol approving signatories. All protocol amendments will be submitted to the relevant institutional IEC/IRB for approval before implementation, as required by local regulations. The only exception will be when the amendment is necessary to eliminate an immediate hazard to the trial participants. In this case, the necessary action will be taken first, with the relevant protocol amendment following shortly thereafter. Once protocol amendments or consent form modifications are implemented at the lead site, Weill Cornell Medicine, updated documents will be provided to participating sites. Weill Cornell Medicine must approve all consent form changes priorto local IRB submission.  
Relevant study documentation will be submitted to the regulatory authorities of the participating countries, according to local/national requirements, for review and approval before the beginning of the study. On completion of the study, the regulatory authorities will be notified that the study has ended.  
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7.3.2 ethical conduct of the

The Investigators and all parties involved should conduct this study in adherence to the ethical principles based on the Declaration of Helsinki, GCP, ICH guidelines and the applicable national and local laws and regulatory requirements.  
This study will be conducted under a protocol reviewed and approved by the applicable ethics committees and investigations will be undertaken by scientifically and medically qualified persons, where the benefits of the study are in proportion to the risks.
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7.3.3 informedconsent

The investigator or qualified designee must obtain documented consent according to ICH-GCP
and local regulations, as applicable, from each potential subject or each subject's legally authorized representative prior to participating in the research study. Subjects who agree to participate will sign the approved informed consent form and will be provided a copy of the signed document.  
The initial ICF, any subsequent revised written ICF and any written information provided to the subject must approved by IRB prior to use. The ICF will adhere to IRB/IEC requirements, applicable laws and regulations.
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7.3.4 compliancewith trial registration and

Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the Food and Drug Administration Amendments Act (FDAAA), the Sponsor-Investigator of the trial is solely responsible for determining whether the trial and its results are subject to the requirements for submission to http://www.clinicaltrials.gov. Information posted will allow subjects to identify potentially appropriate trials for their disease conditions and pursue participation by calling a central contact number for further information on appropriate trial locations and trial site contact information.
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7.3.5 recordretention

Essential documents are those documents that individually and collectively permit evaluation of the study and quality of the data produced. After completion of the study, all documents and data relating to the study will be kept in an orderly manner by the Investigator in a secure study file. Essential documents should be retained for 2 years after the final marketing approval in an ICH region or for at least 2 years since the discontinuation of clinical development of the IP. In addition, all subject medical records and other source documentation will be kept for the maximum time permitted by the hospital, institution, or medical practice.
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7.3.6 data safety and monitoring

A medical monitor is not appointed for this study as the risk level to participants is extremely low.  
Patients are only approached with the express approval of their treating oncologist. Furthermore, co-investigator Dr. Epstein will consult on the suitability of the study for individual patients, when this is in doubt, as well as any unexpected medical events that occur during patients' participation in the study. Participants' responses to study assessments will be monitored for severe psychological distress. Patients' participation will be discontinued if they experience severe distress attributable to the study, as determined by the co-investigators or their treating
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Version Date: April 25th, 2022 physician. Participants may also withdraw from the study at any time with no effect on their treatment. Reporting to *DSMC* Due to the low clinical risk involved in this study, we propose reporting to the Weill Cornell DSMC
on an **annual** basis. Annual reports will comprise: recruitment and retention totals, including voluntary patient withdrawals; a summary of progress since the previous DSMC report; and accounts of any and all adverse events (AEs). For the purpose of this study, an AE is defined as a participant experiencing severe psychological distress,regardless of attribution.
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8. statisticalconsiderations 8.1 sample size/accrual

Phase 1 Interview: Sample size will be 10 clinicians and 10 bereaved caregiversrecruited over 6 months. Phase 2: The pilot clustered RCT will enroll 4medical oncologists(2Oncolo-GIST Version 2.0 trained; 2usual care) and 50 patients(25 will receive care from an Oncolo-GIST Version 2.0- trained oncologist, 25 willreceive usual care) within an 18-month recruitment period. Based on past recruitment yields in the GI and lung cancer clinics at WCM (e.g., recruitment of 60 advanced GI
cancer patients alone in 18 months), we are confident that we can recruit this number of eligible patients within an 18- month period. Given thisis an oncologist communication intervention, we expect the patient drop-out rate to be low. Fifty participants will ensure fairly stable estimates of intervention effects and confidence intervals and indicate if there is a "signal" that the intervention is helpful for promoting prognostic understanding. Using our validated 4-point prognostic understanding score4 as a continuous outcome, if Cohen's d islarge (0.8), with 48 patients and 4 oncologists, the power will be > 80%. If the effect size is medium (0.5), power will drop to 30%.
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8.2 stratificationfactors

25 patients will be recruited to Oncolo-GIST trained clinicians, and 25 patients will be recruited to usual care cliniciansin Phase 2.
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8.3 analysis of endpoints 8.3.1

Phase 1 Interviews: We will obtain feedback on the current version of Oncolo-GIST (Version 1.0).  
Morse's guidelines15 for rigorous qualitative research (e.g., audit trail,saturation) will be followed and Atlas.tisoftware used. 16 Themes emerging will be quantified (re: frequency, priority) and considered to inform revisionsto the Phase 1 Open Trial Oncolo-GIST intervention.  
Phase 2: We will generate preliminary effectsize estimates to inform the planning of the larger, efficacy randomized controlled trial (RCT). Hierarchical Linear Modeling (HLM)17 will be used to evaluate intervention effects. HLM isstatistically appropriate because it accountsfor the clustering of patients within oncologists, creating nonindependence of clustered assessments.  
HLM will model oncologists as a random effect as has been done in prior RCTs.  
18 19 Baseline covariates known to affectstudy outcomes(e.g., patient health literacy) will be included in modelsto increase the precision of effectsize estimates.  
20 This will provide a preliminary effect size estimate of Oncolo-GIST Version 2.0's ability to improve patients' prognostic understanding for a future, largerstudy. Linear and logistic regression models will estimate effects of the
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9. adverse event reporting requirements

Adverse event (AE) monitoring and reporting is a routine part of clinical research. Safety is monitored by evaluation of adverse events reported by subjects or observed by investigators or research staff, as well as by other investigationssuch as clinical laboratory tests, x-rays, electrocardiographs, etc.
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9.1 adverse eventdefinition

An adverse event (also referred to as an adverse experience) can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding),symptom, or disease temporally associated with the use of a drug, and does not imply any judgment about causality. An adverse event can arise with any use of the drug (e.g., off-label use, use in combination with another drug) and with any route of administration, formulation, or dose, including an overdose. In the case of this study, which does not administer any drugs, the only potential AE is psychological distress. Any case ofsevere psychological distress, as indicated by regularstudy assessments(see Section 6.1) or by a participant's self-report, will be noted in the AE log, reported to the IRB, and included in the annual DSMC report. AEs will be reported regardless of attribution, which will be determined by the co-investigators according to the schedule below (section 9.1.1).
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9.1.1 adverse event characteristics and

CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site (http://ctep.cancer.gov).  
- Attribution of the AE:
- Definite - The AE is clearly *related* to the study treatment.  
- Probable - The AE is likely *related* to the study treatment.  
- Possible - The AE may be *related* to the study treatment.  
- Unlikely - The AE is doubtfully *related* to the study treatment.  
- Unrelated - The AE is clearly NOT *related* to the study treatment.
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9.1.2 recording of adverse events

All adverse events will be recorded on a subjectspecific AE log. The AE log will be maintained by the research staff and kept in the subject'sresearch chart.
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9.1.3 reporting of ae to

All AEs occurring on this study will be reported to the IRB according to the IRB policy, which can be accessed via the following link:
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Report ing_Policy.pdf.  
9.1.4 Reporting Eventsto **Participants**
Not Applicable 9.1.5 Events of Special **Interest**
Not Applicable
9.1.6 reporting of pregnancy not
9.1.3 reporting of ae to

10. Unanticipated ProblemsInvolving Risksto Subjects or*Others* Not Applicable 10.1 Definition of Unanticipated ProblemsInvolving Risksto Subjects or **Others(UPIRTSO)**
Not applicable 10.1.1 UnanticipatedProblem **Reporting**
Not applicable
9.1.6 reporting of pregnancy not
11. safety stopping rules

We would stop the study if patientsin the intervention arm became psychologically distressed and their distress was attributable to the way we are training oncologiststo communicate, though it is our hypothesis and aim to demonstrate the emotional and cognitive benefits of our approach. Psychological distressis here defined as self-reported distress on the part of the subject or distress as evaluated by the researcher(defined as an AE in section 7.2.6). As we administer multiple psychometric assessments per interview and enquire about the patient's wellbeing, there is ample opportunity to catch and discuss psychologicaldistress.
9.1.6 reporting of pregnancy not
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OxfordUniversity Press. ISBN 0-19-508536-1.  
2 Elsayyad, Ahmed. "Informed Consent for Comparative Effectiveness Trials". New England Journal of Medicine. 370: 1958–1960.doi:10.1056/NEJMc1403310.  
3 WHO | Informed Consent Form Templates". who.int. Retrieved 14 September 2014 4 Epstein AS, Prigerson HG, O'Reilly EM, Maciejewski PK. Discussions of Life Expectancy and Changesin Illness Understanding in Patients with Advanced Cancer. J Clin Oncol. 2016 Jul 10;34(20):2398-403. doi:
10.1200/JCO.2015.63.6696. Epub 2016 May 23. PubMed PMID: 27217454; PubMed Central PMCID:
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9 Enzinger AC, Zhang B, Schrag D, Prigerson HG. Outcomes of Prognostic Disclosure: Associations with Prognostic Understanding, Distress, and Relationship with Physician Among Patients With Advanced Cancer. J Clin Oncol. 2015; 33(32):3809-16.  
10 Enzinger AC, Zhang B, Schrag D, Prigerson HG. Outcomes of Prognostic Disclosure: Associations with Prognostic Understanding, Distress, and Relationship with Physician Among Patients With Advanced Cancer. J Clin Oncol. 2015; 33(32):3809-16.  
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17 Raudenbush SW, Bryk AS: Hierarchical linear models : applications and data analysis methods(ed 2nd). ThousandOaks, Sage Publications, 2002 18 https://ies.ed.gov/ncer/pubs/20142000/pdf/20142000.pdf 19 Singer JD, Willett JB: Methodological issuesin the design of longitudinal research: Principles and teachers' careers. Educational Evaluation and Policy recommendationsfor a quantitative study of Page \# 16 Analysis 18:265-283, 1996 20 Canner PL. Covariate adjustment of treatment effectsin clinical trials. Control Clin Trials. 1991 Jun;12(3):359-66.PubMed PMID: 1651207.