1. Southeast Clinical Oncology Research Consortium, Inc. (SCOR) Spring Meeting 1 Wake Forest Biotech Place Winston-Salem, NC Saturday, March 21, 2015 8:30 am Funded as an NCI Community Oncology Research Program (NCORP)

2. SCOR NCORP Community Site Leadership PIs: James N. Atkins, MD James D. Bearden, III, MD, FACP Co-PIs: Judith O. Hopkins, MD Patricia C. Griffin, MD

3. SCOR NCORP Community Site Infrastructure Governing Council composed of: PIs Young Investigators Co-PIs Administrator CCDR Coordinator Executive Board composed of: Governing Council 25 “Community Responsible Investigators” Administrative Office Staff

4. SCOR Community Responsible Investigators (CRIs) Anderson: David Griffin, MD William Tomlinson, MD Asheville: Christopher H. Chay, MD Cary: Mark L. Graham, II, MD Charleston: James Orcutt, MD Charlotte: Justin Favaro, MD Danville: Qiwei Gai, MD Florence: Rajesh Bajaj, MD Gastonia: Steven Yates, MD Goldsboro: James N. Atkins, MD Greensboro: James Granfortuna, MD Janak Choksi, MD

5. Greenville: Robert Siegel, MD Hendersonville/Pardee: James Radford, Jr., MD Hendersonville/Park Ridge: Raymond Thertulien, MD High Point: Mohit Kasibhatla, MD Kingsport: Asheesh Shipstone, MD Martinsville: Sreedhar Katragadda, MD Pinehurst: Charles S. Kuzma, MD Richmond: William Irvin, Jr., MD Rock Hill: Sashi Naidu, MD Savannah: James J. Burke, II, MD Spartanburg: James D. Bearden, III, MD, FACP Statesville: Ruby Grimm, MD Winston-Salem: Judith O. Hopkins, MD

6. SCOR NCORP Community Site Young Investigators: Amy E. Curtis, MD Steven M. Duffy, MD Kathleen Elliott, MD Billy J. Irvin, Jr., MD Jeremy Kilburn, MD

7. SCOR Community Sites Anderson, SC Asheville, NC Cary, NC Charleston, SC Charlotte, NC Danville, VA Florence, SC Gastonia, NC Goldsboro, NC Greensboro, NC Greenville, SC Hendersonville, NC/Pardee Hendersonville, NC/Park Ridge High Point, NC Kingsport, TN Martinsville, VA Pinehurst, NC Richmond, VA Rock Hill, SC Savannah, GA Spartanburg, SC Statesville, NC Winston-Salem, NC

8. New Physician Members Kerry Williams-Wuch, MD: Anderson, SC Trevor Austin, MD: Asheville, NC Yanis Bellil, MD: Charleston, SC Kumar Abhishek, MD: Richmond, VA Arvind Bakhru, MD and Jeffrey Kuremsky, MD: Winston-Salem, NC

9. Performance Site Codes Also referred to as NCI CTEP institutional codes Site code designated at registration is the location where the majority of patient assessment (MD visits) for the research study is done. Treatment and/or consenting may be done at another location. SCOR has 42 Components 51 Sub-components

10. Component Definition A hospital, cancer center, physician practice or other institution where patients/participants are enrolled on a regular and ongoing basis to the menu of NCI-approved clinical trials available to the NCORP Community Site. The component may own physician practices, cancer centers, etc. geographically located on the same campus which do NOT have to be classified as a sub-component. Example: Goldsboro, NC has 5 components Wayne Memorial Hospital (Goldsboro) Wilson Medical Center (Wilson) Southeastern Medical Oncology Center/SMOC (Goldsboro) Onslow Memorial Hospital (Jacksonville) Wayne Radiation Oncology (Goldsboro)

11. Sub-Component Definition A practice or organization that contributes to the overall accrual of a component site but is located in a separate geographic location, is part of the component’s business entity, and is managed by the primary component. Example: Goldsboro, NC has 4 sub-components SMOC in Wilson (Component is SMOC) SMOC in Jacksonville (Component is SMOC) SMOC in Clinton (Component is SMOC) Sampson Radiation Oncology (located in Clinton & component is Wayne Rad Onc)

12. Components/Sub-Components 42 components51 sub-components Anderson, SC 10 Asheville, NC26 Cary, NC10 Charleston, SC24 Charlotte, NC82 Danville, VA11 Florence, SC10 Gastonia, NC23 Goldsboro, NC54 Greensboro, NC24 Greenville, SC11

13. Components/Sub-Components 42 components51 sub-components Hendersonville, NC Pardee11 Park Ridge20 High Point, NC21 Kingsport, TN25 Martinsville, VA10 Pinehurst, NC13 Richmond, VA12 Rock Hill, SC11 Savannah, GA14 Spartanburg, SC12 Statesville, NC10 Winston-Salem, NC27

14. Accruals per Community (8/1/14-1/31/15) CommunityRXCCTOTALIndustry Anderson, SC0110 Asheville, NC2112336 Cary, NC8080 Charleston, SC143173 Charlotte, NC3194013 Danville, VA2130 Florence, SC4040 Gastonia, NC430340 Goldsboro, NC267332 Greensboro, NC23204312 Greenville, SC292310 Hendersonville,NC/Pardee 5490

15. Accruals per Community (8/1/14-1/31/15) CommunityRXCCTOTALIndustry Hendersonville, NC Park Ridge 0000 High Point, NC1120 Kingsport, TN6060 Martinsville, VA3470 Pinehurst, NC355581 Richmond, VA96150 Rock Hill, SC0000 Savannah, GA6172 Spartanburg, SC8014940 Statesville, NC2130 Winston-Salem, NC93128 TOTAL28617446047

16. 16 SCOR Accrual Credits Year 01 (8/1/14 – 1/31/15) Community Accruals NCI Assigned Quota Credits RX/CC 507615 Supplemental funding of $150K for 60 extra credits when exceed assigned quota.

17. NCI Funding and Credit System As of March 2, 2015, NCI changed the credits given for base intervention or parent clinical trial registrations Base intervention registrations are now 1.0 credit (previously 1.6 credit) for the majority of clinical trials Credit for ancillary studies are impacted by this alteration in base intervention credits.

18. Example for New Credit Assignment SWOG S1202 Prior CreditNew Credit 1.6 (base intervention) 1.0 (base intervention) Current Payment $2,720.00 0.08 (bio-specimen) 0.05 (bio-specimen) Current Payment $85.00 (the credit and payment will change with new funding sheet from NCI)

19. SCOR Registrations NCTN registrations are thru OPEN Credits for protocols should be given to the research base coordinating the studies

20. Examples Alliance (composed of CALGB, NCCTG, and ACOSOG legacy studies) registrations must be credited to Alliance NRG (composed of NSABP, RTOG, and GOG legacy studies) registrations must be credited to NRG SWOG registrations must be credited to SWOG

21. Other Registrations Registrations done through OPEN for ECOG- ACRIN or NCIC-CTG studies may be credited to any of the following research bases: Alliance NRG SWOG It is best to credit registrations to a specific study to one research base to avoid being audited by multiple research bases

22. Accrual Requirement With the decreased credit assignment of 1.0 for the majority of clinical trials, there will be no individual MD accrual requirement. Community accrual will be assessed on a quarterly basis. Leadership will communicate with communities having no accruals to determine issues being faced and ways to increase accruals.

23. NCI Central Institutional Review Board (NCI-CIRB) SCOR sites still pending NCI CIRB approval Charleston Charlotte Hendersonville/Park Ridge Winston-Salem NCI CIRB participation is a requirement for NCORP sites

24. Travel to Research Base Meetings Any community investigators and research staff that is a member of SCOR may request travel support to research base meetings Travel support is dependent on the NCI funds available Submit request to Debbie Eaton at deaton@southeastclinicaloncology.org

25. Representation at Alliance NCTN Research Base Meetings Alliance:Jim Atkins, MD (med onc) Jay Bearden, III, MD (med onc) Judy Hopkins, MD (med onc) Amy Curtis, MD (rad onc) Billy J. Irvin, Jr., MD (med onc) Caio Rocha-Lima, MD (med onc)

26. Representation at NRG NCTN Research Base Meetings NRG: Jim Atkins, MD (med onc) Jay Bearden, III, MD (med onc) Billy J. Irvin, Jr., MD (med onc) Kevin Roof, MD (rad onc) James J. Burke, II, MD (gyn onc) Volker Stieber, MD (rad onc) Patricia Griffin, MD (rad onc)

27. Representation at SWOG NCTN Research Base Meetings SWOG: Jay Bearden, MD (med onc) Charles Kuzma, MD (med onc) Jeremy Kilburn, MD (rad onc)

28. Representation at Wake Forest NCORP Research Base Meetings Wake Forest:Jay Bearden,MD,(med onc) Judy Hopkins, MD (med onc) Drew Monitto, MD (rad onc) Steven Duffy, MD (med onc) Bob Siegel, MD (med onc)

29. Representation at URCC NCORP Research Base Meetings URCC:Judy Hopkins, MD (med onc) Kathleen Elliott, MD (med onc) Patricia Griffin, MD (rad onc) Jim Atkins, MD (med onc) Jay Bearden, MD (med onc)

30. SCOR leadership and Administrative Office encourage attendance to research base meetings and participation in committee meeting discussions

31. Protocol Highlights Alliance A011202 Alliance A011203 URCC 13059 URCC 13070 (COACH)

32. Alliance A011202 Rand Phase III – comparing ALND to axillary RT in BC patients who have positive SLN disease after neo-adjuvant chemotherapy

33. Eligibility Criteria Pre-Registration or Screening > 18 years Clinical stage T1-3 N1 M0 at diagnosis No inflammatory breast disease No other malignancy w/in 5 yrs Axillary ultrasound w/FNA or core needle bx of ALN documented mets ER/PR/HER2 determined (HER2 + rec’d trastuzumab) Complete all chemo prior to surgery (6 cycles of neo-adj) Clinically neg axilla on PE No neo-adj endocrine/RT/SLN surgery/excisional bx of ln No prior hx of ipsilateral br ca or ipsilateral axillary surgery PS 0-1

34. Eligibility Criteria Intra-operative Registration/Randomization Criteria Breast surg and SLN surg completed w/in 56 days of last chemo Minimum of 1 sentinel node & max of 6 total nodes (sentinel + non-sentinel) id’d & excised by surgeon At least one lymph node w/met greater than 0.2 mm in greatest dimension id’d on intra-op path assessment ALND not performed prior to registration/ randomization

35. Eligibility Criteria Post-op Registration/Randomization Criteria Breast surg & SLN surg completed w/in 56 day of last neo-adj chemo At least 1 lymph node w/met greater than 0.2mm in greatest dimension id’d by H&E staining on final path Among the minimum of 1 & max of 6 nodes id’d & excised by surgeon, no more than 8 lymph nodes found by pathologist For pts undergoing contralateral br surg – if invasive disease found - ineligible

36. A011202

37. A011202 Treatment Arms Arm I : ALND + nodal RT (w/o XRT to dissected axilla) Surg: complete level I & II dissection w/resect of >8 lymph nodes RT: to breast/chest wall, undissected axilla, supraclav nodes & internal mammary in 1 st 3 intercostal spaces – 5d/wk over 5-6 wks Arm 2: Axillary RT & nodal RT only RT: to breast/chest wall, full axilla including levels I/II/III, supraclav nodes, and internal mammary nodes in 1 st 3 intercostal spaces – 5d/wk over 5-6 wks Final surgical pathology findings If negative surgical margins are not achieved at completion of all breast surgeries, then pt will d/c protocol Rx

38. Adjuvant Therapy Adjuvant Endocrine Therapy Pts w/ receptor + disease should receive minimum of 5 yrs endocrine Rx – begin following completion of neoadj Rx & surg, either before/during/after RT Adjuvant Chemo/Biologic/Vaccine Therapy HER2 + disease should complete a total of 1 yr of trastuzumab Rx Chemo/biologic/vaccine Rx in adjuvant setting not allowed Radiation Therapy Begin no earlier than 3 wks and no later than 12 wks following surgery

39. A011202 Ancillary Study Optional Ancillary Study Lymphedema Companion Study

40. Alliance A011203 Rand Phase II – tamoxifen versus Z-endoxifen HCl in postmenopausal women w/metastatic ER+, HER2 – breast cancer Endoxifen is a SERM

41. Eligibility Criteria Pre-Registration Women who agree to under core bx of recurrent/met bc to confirm ER+ and HER2- Previously treated w/ an AI (either letrozole, anastrozole or exemestane) either in the adjuvant or met setting and have one of following types of primary or secondary endocrine resistant dis. Primary Clinical Resistance – one of following: 1. Recurrence w/in 1 st 2 yrs of adj endocrine Rx while on endocrine Rx 2. Prog w/in 1 st 6 months of initiating 1 st -line endocrine Rx for Rx of met dis Secondary Clinical Resistance – one of following: 1. Recurrence during yrs 2-5 of adj endocrine Rx (or w/in 12 mos of completing adj endocrine Rx) 2. Prog occurring >6 months after initiating endocrine Rx for met dis while on endocrine Rx

42. Eligibility Criteria (Pre-Reg) Cont. Hx of meas disease by RECIST criteria No hx of tumors involving spinal cord or heart No hx of visceral crisis, lymphangitic spread or brain mets > 18 yrs Postmenopausal verified by: prior bilat surg oophorectomy OR > 60 yrs OR < 60 yrs w/no menses for < 1 yr w/FSH & estradiol levels w/in menopausal range < 2 prior chemo regimens in met setting Prior Rx w/AI either in adj/met setting is required No current meds or substances that are strong inhibitors of CYP2D6

43. Eligibility Criteria (Pre-Reg) Cont. No other IND agents No uncontrolled intercurrent illness No co-morbid conditions No other active 2 nd malignancy PS 0-2 Able to swallow oral formulation of study agent Required laboratory values: Hgb >9 g/dL Platelet count > 75,000/mm 3 Creatinine and total bili < 1.5 x ULN AST < 2.5 x ULN

44. Eligibility Criteria - Registration Measurable dis as by RECIST criteria No tumors involving spinal cord or heart No visceral crisis, lymphangitic spread or known brain mets Histo confirm from bx ER+ and HER2- No prior therapy allowed < 2 weeks prior to regis (includes chemo, immunotherapy, biologic therapy, hormonal therapy, monoclonal antibodies, RT or anti-HER-2 or other targeted therapy)

46. A011203 Treatment Arms Cycle = 21 days Arm I: Z-Endoxifen HCl 80 mg PO days 1-21 Arm II:Tamoxifen 20 mg PO days 1-21 Crossover to Z-Endoxifen HCl for Arm II disease progression Re-register to study w/in 14 days of progression documentation

47. A011203 Ancillary Studies All are optional Bio-specimen – formalin fixed tissue from breast core biopsies Bio-specimen – blood for CTC, cfDNA, and bone turnover studies Bio-specimen – blood for PG and PK studies

48. URCC 13059 A Geriatric Assessment Intervention for Patients Aged 70 and Over Receiving Chemotherapy for Advanced Cancer: Reducing Chemotherapy Toxicity in Older Adults Each site will be randomized to intervention vs no intervention

49. Eligibility Criteria – Physicians Must work at NCORP Community Site No plans to leave NCORP practice or retire at time of enrollment

50. Eligibility Criteria - Participants Male or female ≥ 70 years of age with history of cancer Diagnosis of advanced solid tumor – in most cases stage IV malignancy Received recommendation for first line treatment with chemo by primary oncologist Have at least one geriatric assessment domain impaired other than polypharmacy

51. Eligibility (Cont) Not previously received chemo, monoclonal antibody therapy or targeted therapy for current diagnosis of ca Plan to start chemo within 4 weeks Plan to be on chemo > 3 months Able to provide informed consent Adequate understanding of English language

52. Eligibility (Cont) No planned regimen not including chemo No surgery/RT planned within 3 months of consent No brain mets Must have decision-making capacity AND have designated health care proxy

53. URCC 13059 Intervention Site (Arm 1) VS Usual Care Site (Arm 2)

54. URCC 13059

55. URCC 13070 (referred to as COACH) Improving Communication for Cancer Treatment: Addressing Concerns of Older Cancer Patients and Caregivers Evaluates whether Geriatric Assessment (GA) summary plus GA-driven recommendations can improve patient satisfaction with communication regarding age-related issues between patients, oncologists, and caregivers.

56. Study Subjects Include: 1.Oncology Physicians at NCORP site 2.Patients 3.Caregivers

57. Eligibility Criteria: Oncology Physicians Must work at NCORP practice site with no plans to leave or retire at the time of enrollment into the study Agree to participate either via Research Electronic Data Capture (REDCap) or on paper Will provide baseline demographic information Will fill out baseline survey to evaluate preferences for decision-making Will help identify patients

58. Eligibility Criteria: Patients Male or female 70 years of age or older Diagnosis of an advanced solid tumor or lymphoma – in most situations, stage IV cancer Must be considering or currently receiving any kind of cancer treatment Have at least one geriatric assessment domain meet the cut-off score for impairment other than polypharmacy

59. Eligibility Criteria: Patients(Cont) Have visits planned with oncologist for at least 3 months and willing to come for study visits Adequate understanding of English No surgery planned within 3 months of consent Not made a decision to not undergo any cancer treatment

60. Caregivers Caregiver can be anyone, age 21 or older, who is able to understand spoken English, understand the study process, and provide informed consent. One caregiver for each patient will be eligible and must be chosen by the patient.

61. Eligibility Criteria: Caregivers Selected by the patient Can be health care proxy Caregivers must be able to understand the consent form and have no cognitive, health or sensory impairment

63. Discussion of SCOR Fall Meeting There is plans to have Governing Council and Executive Board meetings Piedmont Oncology Conference September 10-12, 2015 Renaissance Hotel Asheville, NC

64. SCOR Cancer Care Delivery Research Update Lucy Gansauer, RN, MSN SCOR CCDR Coordinator March 21, 2015

65. Cancer Care Delivery Research NCORP requires a least one site to participate in CCDR SCOR has two sites ▫ Gibbs Cancer Center at Spartanburg Regional Medical Center ▫ Novant Health Forsyth Medical Center

66. NCI Update CCDR is new focus for NCI NCI is figuring out the program Still a lot of unanswered questions NCI Committees ▫ CCDR Steering Committee- Review approved study concepts ▫ CCDR Coordinating Committee  Determine CCDR priorities  Metrics of participations

67. NCI Committees CCDR Steering Committee-still forming CCDR Coordinating Committee – SCOR representatives ▫ Judith Hopkins, MD (URCC Representative) ▫ Lucy Gansauer, RN, MSN (Community Representative) CCDR Metrics of Participation Working Group ▫ Lucy Gansauer (Community Representative)

68. SCOR CCDR Committees SCOR CCDR Committee James Bearden, MD Judith Hopkins, MD Susan Tuttle, RN Lucy Gansauer, RN, MSN SCOR CCDR Site Coordinating Committee Lucy Gansauer, RN, MSN (Gibbs) – Lead Coordinator Gibbs CCDR Staff Dena Webb (Novant) – Lead Coordinator Novant CCDR Staff

69. Capacity Assessment Research Bases are required by NCI to conducting capacity assessment ▫ Sites will be asked to respond to questionnaires or data requests ▫ Sites are encouraged to respond to these requests ▫ Copy the SCOR Administrative Office when sending in the information ▫ We can count this work as effort towards CCDR

70. Research Base Activity Alliance CCDR Committee Judith Hopkins, MD Lucy Gansauer, RN, MSN James Bearden, MD NRG CCDR Committee Lucy Gansauer, RN, MSN SWOG CCDR (still forming) URCC (heavily engaged in CCDR type of studies) Judith Hopkins, MD Lucy Gansauer, RN, MSN Dena Webb Wake Forest CCDR Committee Judith Hopkins, MD Lucy Gansauer, RN, MSN James Bearden, MD

71. CCDR Research Questions Research Bases are looking for good research questions from the community sites Dr. Hopkins and Lucy Gansauer have submitted CCDR study concepts to Alliance, URCC, Wake Forest, and NRG

72. Next Year No CCDR studies approved currently by NCI Anticipate CCDR studies coming in Fall 2015 ▫ NRG is developing a study with Kaiser Permanente NCORP ▫ Not sure what other studies are in the pipeline Anticipate request for capacity assessment related to site ability to mine data at each site

73. The following presentation is not part of the NCORP funding and is outside of the SCOR organization

74. Regulatory Support Services Oncology Research Success

75. Providing Regulatory Services:  IRB submissions  Managing all regulatory documents  Compliance with federal research requirements  Provide Human Subjects Protection Training (CITI) Oncology Research Success

76.  Are your Coordinators doing regulatory work?  Do they feel confident addressing regulatory requirements?  Do they need time to ensure timely and quality data?  Do they need more time for screening & accruals?

78. Oncology Research Success Component of Spartanburg Regional Healthcare System Established program - 30 years of experience Specialized regulatory staff SoCRA certified Experienced: NCI CIRB Central IRBs - WIRB, Quorum, and others Serving diverse organizations’ regulatory needs Utilizing: Web-based storage of regulatory documents Remote access to all essential documents for your staff

79. Oncology Research Success Site: 11-20 protocols open 6-11 investigators Requesting support for only NCI CIRB trials Services requested include: -NCI CIRB application process -Development and maintenance of site-specific boilerplate language -Annual maintenance of local context and PI forms with NCI CIRB -Reporting of IRB decisions to SCOR -Internal SAE and Protocol Deviation assessment and reporting -Tracking and maintenance of staff training requirements -Management of all regulatory documents Annual Fee of $10,000

80. For more information, contact: Heather Farmer, MS, CCRP Gibbs Cancer Center & Research Institute 864-560-1060 hfarmer@gibbscc.org Oncology Research Success Site: 11-20 protocols 6-11 investigators Requesting support for trials with any IRB Services requested include: Development of consent template and local context with external IRBs Initiation, Amendments, and Renewals applications Development of site-specific recruitment materials Reporting of IRB decisions to SCOR External & Internal SAE plus Protocol Deviation assessment & reporting Tracking and maintenance of staff training requirements Management of all regulatory documents Annual Fee of $18,000

81. For more information, contact: Heather Farmer, MS, CCRP Gibbs Cancer Center & Research Institute 864-560-1060 hfarmer@gibbscc.orghfarmer@gibbscc.orgg  We will create a customized program for your site.  Annual fees customized to size and scope of programs  Fees ranging from $5,000 to $20,000 Free assessment without obligation