Dr. Dawn L. Hershman of the Herbert Irving Comprehensive Cancer Center at Columbia University presented the basics of clinical trials and emphasized how important it is for more patients to participate in them. She also discussed trials currently available for early stage and metastatic breast cancers. The webinar was presented on June 25, 2014. To hear the webinar, visit www.sharecancersupport.org/hershman

1. WHY SHOULD I JOIN A CLINICAL TRIAL?
Dawn Hershman, MD, MS
Associate Professor of Medicine and Epidemiology
Leader, Breast Caner Program
Herbert Irving Comprehensive Cancer Center
Columbia University Medical Center
NCI Community Oncology Research Program
SWOG – Research Base Co-PI

2. What is a clinical trial?
• Clinical trials look at new ways to prevent,
detect, control or treat disease.
• The GOAL is to find if a new test or therapy
is safe and effective.
• It is important to have many types of people
with different ages, races, ethnicities, and
genders to see how different people respond
to a treatment
http://www.nih.gov/health/clinicaltrials/basics.htm

3. What is a clinical trial?
• Participants are assigned to receive one or more
interventions (or no intervention)
• Researchers evaluate the effects of the
interventions on biomedical or health-related
outcomes.
• The assignments are determined by the study
protocol.
• Participants may receive a drug, treatment,
procedure, or other types of interventions.
http://clinicaltrials.gov/ct2/about-studies/glossary#C

4. Clinical Research Categories
• Interventional
• Observational
• Ancillary
• Correlative

5. Interventional
• Individuals are assigned to receive
intervention
• Drug, Device or Other (ie behavioral)
• Diagnostic, Therapeutic, Supportive Care
• Assignment may or may not be random
• Participants are followed and a health
outcome is assessed

6. Observational
• Involves no intervention or alteration of the
status of the participant
• Biomedical or health outcomes are assessed in
a pre-defined group of participants
• Participants may or may not receive the
intervention
• The investigator is not responsible for
assigning the specific intervention

7. Observational Studies vs. RCTs
Armstrong, K, JCO 2012;30: 4208-42144

8. Strengths Observational Studies
• Examine “real world” populations
– Diversity increases generalizability
• Large numbers of participants
• Leverage existing data
• Includes vulnerable populations
• Power to find a dose response relationship
• Can be completed more quickly with less
cost

9. Limitations of Observational Data
• Selection Bias
• Systematic error in the ascertainment of study subjects
• Intervention groups differ in characteristics that are
associated with the outcome of interest
• Performance Bias
• The delivery of one type of intervention is associated with
generally higher levels quality of care
• Detection Bias
• Outcomes of interest are more easily detected in one
group than another

10. Ancillary/Correlative
• Ancillary
– Stimulated by a main clinical trial to answer
secondary question
– Includes patients accrued to the main study
• Correlative
– Laboratory based
– Use specimens that exist
– Used to assess risk, outcomes, response

11. What are the types of clinical trials?
Diagnostic: Protocols designed to evaluate
interventions aimed at identifying a disease or health
condition
Prevention: Protocols designed to assess
interventions aimed at preventing the development of
a disease or health condition
Screening: Protocol designed to examine methods for
identifying a condition or risk of a condition in people
not known to have the condition
http://www.nih.gov/health/clinicaltrials/basics.htm

12. What are the types of clinical trials?
Treatment: Protocol designed to evaluate
interventions for treating a disease
Supportive Care: Protocol designed to evaluate
interventions to maximize comfort, minimize side
effects or prevent the decline in a health condition
Health Care Deliver: Protocol designed to
evaluate the delivery, processes, management,
organization or financing of healthcare
http://www.nih.gov/health/clinicaltrials/basics.htm

13. Clinical trial stages

14. Pre-clinical stage
• A new drug or treatment is
tested using animals to
determine if it is safe for
humans

15. Phase I
A new treatment is tested in a small
number of people to see how safe it is
and what are its side effects
Involves 20-80 subjects

16. Phase II
A treatment is given to a larger number of
people to see its effectiveness and safety
Involves 100-300 people

17. Phase III
A treatment is tested in large number of
people to prove that it is effective, check
side effects, compare it to other
treatments and get safety information
Involves 1,000-3,000 people

18. Phase IV
A treatment is now approved by the FDA
and available to the public but its usage,
risks and benefits are still monitored

19. What is a clinical protocol?
• Studies are led by investigators who write the
study protocol
• Protocols describe:
– Who can participate
– The length of the study
– What they will receive
– What information is collected
http://www.nih.gov/health/clinicaltrials/basics.htm

20. What is a clinical protocol?
Eligibility criteria are an important part of the
protocol
• Criteria often include:
– Age
– Gender Often not everyone
– Type of disease meets criteria for
– Stage of disease participation
– Previous treatment
– Medical conditions
http://www.nih.gov/health/clinicaltrials/basics.htm

21. How does a clinical protocol
become approved?
• Once an idea is formulated and the
protocol written it must be reviewed
• All clinical trials in the US are approved
and monitored by an Institutional Review
Board (IRB)
http://www.nih.gov/health/clinicaltrials/basics.htm

22. What is an IRB?
An IRB is an independent committee of
doctors, statisticians, and community
members who review a study’s safety,
human rights, and ethics

23. Informed consent

24. Informed consent
• Understanding the procedures involved,
risks and benefits of a study are extremely
important when making decisions
• The informed consent document and
discussion are used to help you in this
process
• Translation and interpretive services are
available during this time
http://www.nih.gov/health/clinicaltrials/basics.htm

25. Clinical trial concepts
• Placebo: Inactive product that is very similar to
the real drug or treatment but does has no
affect on the condition
• Randomization: A person is randomly
assigned to one of any treatments in a study.
Done to avoid bias or influence on the outcome
• Single or double blinding: the subject doesn’t
know the treatment (single) the subject and
researcher do not know the treatment (double)
http://www.nih.gov/health/clinicaltrials/basics.htm

26. What happens once the clinical trial
is over?
• Analysis: All collected information is analyzed
to see if there are any differences between
treatment groups
• Peer review: Experts review the analysis to see
it is sound
• Publication: Once it is past peer review it is
published in a scientific journal
http://www.nih.gov/health/clinicaltrials/basics.htm

27. Why should I take part in a clinical trial?
1. Access to a new
intervention that’s not
normally available.
2. A new intervention may
improve your health.
3. Most studies cover the
cost of the intervention.
4. You are helping
researchers answer
questions about a disease.
5. You play an active role in
your own health care.
1. A new intervention may not
be better than the standard.
2. A new intervention has
risks and side effects.
3. Your health insurance may
not cover all costs.
4. If you are in a randomized
study you will not be able to
choose the intervention you
receive.
5. You may need to make
more visits to the clinic or
hospital.

29. NCI Clinical Trials
• NCTN – National Clinical Trials Network
• NCORP -NCI Community Oncology
Research Program

30. NCI Supports Community-Based Cancer
Research
• Majority of cancer care is provided in the
community
• Access to large diverse patient populations
• Access to real world healthcare delivery
settings
• Test feasibility of new interventions/processes
• Engage community oncologists in the
research process to accelerate the uptake of
evidence-based practice

31. NCTN

32. NCI Funding for NCTN

33. NCORP Research Expansion

34. Division of Cancer
Control and Population
Sciences (DCCPS)
NCORP Associate Director
Center to Reduce
Cancer Health
Disparities (CRCHD)
Division of Cancer
Treatment and
Diagnosis (DCTD)
Division of Cancer Prevention
(DCP)
NCORP Director
NCORP Organizational Structure
NCI
NCORP
Research Bases:
NCTN Groups
Cancer Centers
Cancer Prevention
and Control Trials
Cancer Care
Delivery
Community Sites:
NCORP
NCORP-Minority/
Underserved
Cancer Prevention
and Control Trials
Treatment Trials
Cancer Care
Delivery
Extramural Investigators
NCI-designated Cancer Centers
Other Academic Centers
Health Care Organizations
Nonprofit Research
Organizations
Clinical Trials and
Translational Research
Advisory Committee (CTAC)
Coordinating Center
for Clinical Trials
Evaluation and Prioritization
of Research Concepts
Steering Committee:
Disease specific
Symptom mgt./QOL
Cancer Care Delivery
Central
Institution
Review
Board
CIRB
Cancer
Trials
Support
Unit
CTSU
National Clinical
Trials Network
(NCTN)
Treatment Trials

35. Cancer prevention trials
TARGET = Prevent breast cancer recurrence
OR prevent breast cancer
• DHA or placebo to prevent recurrence in breast
cancer survivors
• Vitamin D or placebo in premenopausal women
at high risk for breast cancer
• BFIT: 1st degree female relatives of breast
cancer survivors receive an educational
intervention

36. Cancer treatment trials
FOCUS = Receive intervention before
OR after surgery
• Receive propanolol prior to breast surgery to
determine its effect on tumor growth
• Receive metformin and atorvastatin prior to
breast surgery to determine its effect on tumor
growth

37. Cancer treatment trials
FOCUS = Receive intervention before
OR after surgery
• (B47) Randomly receive 1 of 4 chemotherapies
after surgery
• (B50) Receive a drug called TDM1 or Herceptin
if breast disease is still present after surgery and
received treatment prior to surgery
• (S1207) Receive a drug called everolimus for
high risk hormone positive and HER2 negative
disease

38. Metastatic treatment trials
FOCUS = Receive intervention to prevent
disease proliferation
• Triple negative breast cancer patients:
metformin and erlotinib
• Metastatic patients with hormone sensitive Her2
Negative. Letrozole +/- palbocyclib

39. Metastatic treatment trials
• Metastatic Her-2 positive randomized to
lapatinib + Xeloda vs. Neratinib + Xeloda
• Bollero 4 – everolimus/letrozole +/- RAD Y24135
• LY2835219 – hormone sensitive her-2 negative
• PD-L1 – Phase 1
• Her2 + - trastuzumab/ruxolitinib

40. Symptom management trials
FOCUS = Receive intervention to address
side effects
• True, sham or no acupuncture to treat joint pain
caused by hormonal therapy
• True or sham electroacupuncture to treat
numbness during taxol chemotherapy
• Menthol cream or placebo to treat numbness
after chemotherapy

41. Cancer survivorship trials
FOCUS = Gather information on the
physical & mental health of survivors
• Exercise and Dietary intervention to decrease
weight and improve outcome

42. How do I find out about trials?
• ONCOLOGISTS
– ASK YOUR ONCOLOGIST - They are familiar with
clinical trials resources, websites, and contacts
• COMMUNITY RESOURCES
– Local support groups
– American Cancer Society
• INTERNET
– All trials are registered in the US and worldwide on
clinicaltrials.gov
• FRIENDS & FAMILY