1. NRG Oncology NCORP Lisa Kachnic MD, FASTRO Associate Chair
NRG Oncology Semi-annual Meeting
New Investigators Meeting
January 10, 2020

2. What is Cancer Control Research?
Cancer control research is the conduct of basic and applied investigation in the behavioral, social and population sciences to create or enhance interventions that, independently or in combination with biomedical approaches, reduce cancer risk, incidence, morbidity and mortality, and improve quality of life.
Cancercontrol.cancer.gov accessed

3. NCI Community Oncology Research Program (NCORP) Network
The NCI NCORP is a national network that brings cancer clinical trials and care delivery studies to people in their own communities. Their focus areas include:
Cancer Control and Prevention
Symptom Management
Screening
Post-Treatment Surveillance
Quality-of-Life Studies Embedded in Treatment Trials
Cancer Care Delivery
Cancer Disparities

4. NCI NCORP Network Structure
The NCORP is housed in the NCI Division of Cancer Prevention, with collaboration by the NCI Division of Cancer Control and Population Sciences, NCI Division of Cancer Treatment and Diagnosis and NCI Center to Reduce Cancer Health Disparities
NCORP is comprised of 7 Research Bases and 46 Community Sites, 14 of which are designated as Minority/Underserved (MU) Community Sites
NCORP MU Community Sites have a patient population comprised of at least 30% racial/ethnic minorities or rural residents
The NCORP Community Sites accrue participants to NCI-approved cancer clinical trials
The sites are consortia of researchers, public hospitals, physician practices, academic medical centers, and other groups that provide healthcare services in communities across the U.S

6. Overall NCI NCORP Accrual by Year 8/1/14 – 10/31/18
Total: 26,954
It is important to note that 30% - 35% of the patients enrolled on NCTN clinical trials, including precision medicine studies, are from NCORP sites

7. NRG Oncology NCORP Structure
NCORP Operations
Committee
Ca Prevention and Control Research (CPCR) Co-Chairs: L Kachnic, D Levine
Vice Chairs: D Barton, J Bauman
- Neurocognitive Function
Gender-specific Symptom Mgmt
Behavioral Interventions
Dose Alterations
Ca Risk Reduction
Health Disparities Research (HDR)
Chair: K Yeager
Vice Chair: C Hughes
Racial/Ethnic Minorities
Elderly
Rural Populations
Patient Centered Outcomes Research (PCOR)
Chair:
B. Movsas/
Vice Chairs
L. Wenzel, P Ganz
- PROs tx trials
- Consult on PROs in CCC, CPC, CCD, HDC trials
NRG
NCORP Finance Committee

8. NRG NCORP Core Grant Aims and Priorities
Four symptomatic management themes:
neurotoxicity
cardiotoxicity
lymphedema
inflammation
Cancer prevention, survivorship and palliative interventions
Cancer care delivery
Cancer disparity research, in collaboration with our Health Disparities Research (HDR) Program

9. NRG NCORP Changing Standard of Care
Major changes over this past grant period:
R0614: Memantine during whole brain RT reduces neurocognitive deterioration
R0933: Hippocampal avoidance during whole brain RT leads to HVLT preservation
R1203: IMRT reduces bowel toxicities (over 3D RT) from the patient perspective in postop GYN cancers

10. Sig. neurocog. differences favoring memantine arm for:
Brown et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy (RTOG 0614): A randomized, double-blind, placebo-controlled trial.
Neuro Oncol. 2013;15(10):
Gondi et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): A phase II multi-institutional trial.
J Clin Oncol. 2014;32(34):
Cumulative incidence of cognitive function sig. improved In Memantine arm.
Hopkins Verbal Learning Test (HVLT) scores sig. improved over historical controls for 50 pts alive at 6 mos.
Sig. neurocog. differences favoring memantine arm for:
COWA scores at 8 (P = .008) and 16 weeks (P = .0041)
TMT-A and MMSE at 24 weeks (P = and .0038, respectively),
HA-WBRT (IMRT) for pts with brain mets associated with sig. prevention of HVLT-R DR decline, compared with prespecified historical controls of WBRT without HA
FACT-BR emotional well being improved over time (P = .042). Other FACT-BR domains and ADL scores remained stable.
Only 4.5% experienced progression in the hippocampal avoidance area vs, historic 8.6%
The significantly positive findings for both of these intervention were combined/informed the current generations of trials.

11. Baseline neurocognitive assessment: HVLT-R, TMT, COWA
CLOSED NRG-CC001: A Randomized Phase III Trial of Memantine and Whole-brain Radiotherapy with or without Hippocampal Avoidance in Patients with Brain Metastases
SCHEMA
STEP 1 REGISTRATION
STRATIFICATION
RPA Class:
1. Class I
2. Class II
Prior therapy:
1. None
2. Radiosurgery or surgical resection*
STEP 2 REGISTRATION
Baseline neurocognitive assessment: HVLT-R, TMT, COWA
RANDOMIZATION
Arm 1
WBRT 30 Gy/10 fractions
+ Memantine**
Arm 2
WBRT with Hippocampal Avoidance using IMRT 30 Gy/10 fractions + Memantine**

12. Small Cell Lung Ca Stage Concomitant Memantine
OPEN NRG-CC003: Phase IIR/III Trial Prophylactic Cranial Irradiation with or without Hippocampal Avoidance for Small Cell Lung Cancer
Stratify
Randomi ze
PCI 25Gy/10
Small Cell Lung Ca
Stage
Concomitant Memantine
HA-PCI 25Gy/10
Basic Eligibility: Small cell lung cancer; PR or CR to chemo; ECOG PS≤70; MRI scan
Sample Size: Phase IIR: 172 patients Phase III: 304 patients
Primary Endpoints: Phase IIR—Intracranial relapse rate at 12 months
Phase III—HVLT-R delayed recall deterioration at 6 months
Statistical Design: Phase IIR: Non-inferiority margin of >20% difference; 164 analyzable pts
Phase III: 29% with PCI vs. 14.5% with HA-PCI; 198 analyzable pts

13. Brain Mets from Small Cell Lung Ca
Developing NRG-CC1974: Phase III Trial Stereotactic Radiosurgery versus Hippocampal-Avoidant Whole-Brain Radiotherapy for Brain Metastases from Small Cell Lung Cancer
Basic Eligibility: Small cell lung cancer; ≤10 brain mets≤3cm; total vol 30cc; KPS≥70
Randomi ze
Stratify
SRS alone
Brain Mets from Small Cell Lung Ca
DS-GPA
Exposure to NCF Testing*
HA-WBRT Gy/10
*Pts enrolled on SWOG trial will have been exposed to NCF Testing
Sample Size: 200 patients
Primary endpt: Time to cognitive failure--HVLT-R, COWA, and TMT A and B
Basic Statistical Design:
Cognitive fxn failure 58.8% at 6 mos with HA-WBRT+mem vs. 41.8% at 6 mos with SRS.
150 analyzable pts

14. Completed NRG NCORP Trials
Study
Disease
Date Closed
G0273
Chemo tolerance in elderly patient
6/4/2014
G0244
Lymphedema incidence, risk factor and impact
11/17/2014
B-43
RT vs. RT+Trast
12/8/2014
R1203
3D vs. IMRT for pelvic RT
8/27/2015
NRG-CC002
Elderly post-op outcomes
11/2/2015
NRG-CC001
Memantine + WBRT w/ or w/out HA in pts w/ Brain Mets
3/12/2018
G225
Diet and Exercise to Prevent Ovarian Cancer Recurrence
8/24/2018
G237
CA-IX, p16, PHV for Dx of AGUS in Cervical Cancer
8/2/2019
The completed NRG CPC trials are listed; it is important to note that NCORP sites are our leading accruers for treatment and CPC trials.

15. Ongoing NRG NCORP Trials **accrual as of December 31, 2019
Study No
Disease Site
Description
Date
Activated
Target
Accrual
Total Accrual
NCORP Accrual (%)
Expected
Closure
GOG
278
Cervix
Physical fx & QOL before/after non-radical surgery
10/1/12
220
199
<1%
Aug
2020
NRG 
CC003
Lung
Seamless Ph II/III PCI vs. PCI with hippocampal sparing for cognitive fx
12/7/15
172 (II)
302 (III)
176 of 172 (II)
266 of 302 (III)
30%
Phase II complete: Re-opened to Phase III accrual Jan 2019
CC004
Breast, GYN
Ph II Bupropion trial testing 150 vs 300 mg to improve sexual desire more than placebo
5/31/17
234
219
100%
March 2020
CCD007
Prostate
Survivorship care plan for prostate ca survivors on ADT to increase blood glucose and cholesterol checks in yr 2 after starting ADT & lower CVD risk
03/27/19
504 21 0%
October 2021

16. Developing NRG NCORP Trials
Study No
Disease
Comments
NRG-CC005
Forte – Five or Ten Year Colonoscopy for 1-2 Non-advanced Adenomatous Polyps
Protocol submitted to DCP
NRG-CC008
A Non-Randomized Prospective Clinical Trial Comparing the Non-Inferiority of Salpingectomy to Salpingo-oophorectomy to Reduce the Risk of Ovarian Cancer Among BRCA1 Carriers [SOROC]
Protocol pending CIRB and DCP final approval
NRG-CC1974
SRS vs. HA-WBRT for 10 or fewer Brain Metastases from Small Cell Lung Cancer
Concept submitted to DCP
FORTE if approved, will provide cancer control credits for entry plus additional credits for each year of follow-up. It should be an excellent way for NCORP sites to meet their cancer control requirements. N= The primary endpoint for the trial is the incidence of CRC.

17. NRG NCORP Concept Development Guidelines
All new NCORP concepts must be reviewed and vetted by the appropriate Cancer Prevention and Control, Cancer Care Delivery Research or Health Disparities committees
High priority concepts will then be presented by the committee co-chairs to the NCORP PIs at monthly strategy meetings
Those felt to be most meritorious are invited to move on to the NCORP formal concept review process

18. NRG NCORP Concept Review Process
Concepts considered for NCORP formal concept review have been presented and supported by the relevant NCORP committee; NRG disease site committee and seen by NRG statistician to comment on potential sample size
Concepts are distributed and assigned to appropriate reviewers for content, PROs, TRP, Stats, pt advocate, community feasibility and will obtain written comments
At NCORP steering committee face-to-face meeting (or conference call), PI may introduce study in a few sentences, no slides permitted. Reviewers will present comments and recommendations.
Call for concepts will be sent to all NCORP
Committees with submission deadline
Concepts meeting the requirements above are submitted to on the NCORP concept submission form
Approval
Revise and Resubmit
Disapproval
If approved, present to NRG Research Strategy Committee/CPAC, upon approval submit to NCI submission
Revise proceed through re-review as above
End

19. How to Become a Member
CPC and CCDR Committees are soliciting new members beginning January 2020
Watch for NRG broadcast announcement after the meeting!

20. Other Opportunities Seed Grant Pipeline & ‘Buddies’
Seed grant announcement mid-February 2020
Will Incorporate New Investigator Mentee on Protocols
Travel Grants
Call for applications 8-10 weeks prior to each semiannual meeting
Secondary Analyses

21. Questions?