Audio and slides for this presentation are available on YouTube: http://youtu.be/NzJ_fvSxwGk Sara Tolaney, MD, MPH, a breast oncologist with the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, gives an overview of phase I clinical trials and some of the new drugs being tested to treat breast cancer. This talk was originally given at the Metastatic Breast Cancer Forum at Dana-Farber on Oct. 5, 2013.

1. Phase I Clinical Trials
Sara Tolaney, MD, MPH
Breast oncologist
Susan F. Smith Center for Women’s Cancers at
Dana-Farber Cancer Institute
October 5, 2013

2. What are clinical trials?
• Research studies that are designed to answer
questions about new ways to treat cancer

3. What are the different types of clinical trials?
Phase
Purpose
Phase I
Determine dose
Determine side-effects
(Number of people: 15-20)
Phase 2
Determine efficacy
(Number of people: <100)
Phase 3
Compare the new treatment to a
standard treatment
Number of people: 100-1000s)

4. Road To FDA Approval
Preclinical
Phase 1
Phase 2
Phase 3
FDA
Approval

5. Goals of Phase 1 Clinical Trials
• How much of a new drug can be given safely
• How often the drug needs to be given
• What are the side effects of the new drug

6. Types of Phase 1 Trials
• Disease specific phase 1 studies
• All-comer phase 1 trials open to any solid
tumor
• New agent alone
• Combining new agents
• Combining new agent with standard
chemotherapy

7. Dose Escalation in Phase 1 Studies: 3+3 Design
Once dose
determined
30 mg
20 mg
10 mg
3 Patients
3 Patients
3 Patients
EXPANSION COHORT
Enroll 10-20 patients

8. Pharmacokinetics (PKs)
• Tests how rapidly a drug is cleared from
circulation
• Challenging for patients because can
sometimes require long days and multiple
visits a week during the first cycle of therapy

9. Early Drug Development Center
(EDDC)
• Conducts research dedicated to studying new drugs
• Specializes in phase I clinical trials
• Has over 30 phase I studies, some of which are open to
patients with all solid tumors, and a few of which are
specific to breast cancer
• You may be referred to the EDDC to discuss trial
possibilities
• If you go on a study, you will be followed within the
EDDC, but will also continue to have your original
oncologist/team involved in your care

10. Trials of Interest for Breast Cancer
• BRCA Carriers
– Rucaparib
– Veliparib and Irinotecan
– Sapacitabine and Seleciclib
• ER+ Breast Cancer
– Cdk 4/6 inhibitors
• Triple-negative Breast Cancer
– Mek/akt
– Cdk/parp
– PDL1 Antibody (immunotherapy)

11. PARP Inhibitors
Igelhart JD and Silver DP. NEJM 2009

12. PARP Inhibitor Studies
• Rucaparib
– PARP inhibitor given alone
• Veliparib + Irinotecan
– PARP inhibitor given with chemotherapy
• Olaparib + BKM120
– In breast cancer group, combines PARP with PI3K
inhibitor

13. Sapacitabine + Seleciclib
• Sapacitabine: oral chemotherapy
• Seleciclib: oral cdk 1,2, 7, 9 inhibitor

14. CDK 4/6 Inhibitors

15. Progression-Free Survival
Progression-Free Survival Probability
PD 991 + LET
(n = 84)
LET
(n = 81)
1.0
Number of Events (%)
21 (25)
40 (49)
0.9
Median PFS, months
(95% CI)
26.1
(12.7, 26.1)
7.5
(5.6, 12.6)
0.8
Hazard Ratio
(95% CI)
0.7
P value
0.37
(0.21, 0.63)
<0.001
0.6
0.5
0.4
0.3
0.2
0.1
0
0
2
4
6
8
10
84
81
75
57
60
38
14
16
18
20
22
24
26
14
4
9
3
5
3
3
1
1
1
Time (Month)
Number of patients at risk
PD991+LET
LET
12
53
29
43
22
35
17
25
11
18
6
15
5
28

16. Ongoing studies with cdk 4/6 inhibitors
• LEE011
– Cdk 4/6 inhibitor given alone, in expansion phase
• Lilly cdk 4/6 inhibitor + faslodex

17. Triple-negative Breast Cancer
• PI3K inhibition
– GDC-0973/GDC-0068 (MEK/Akt inhibitors)
– BKM120 (phase 2)
• Dinaciclib/Veliparib
– Cdk + PARP
• Immunotherapy
– PDL1 Antibody

18. Conclusions
• Exciting time in drug development
• Several phase I clinical trial options for
patients with varying subtypes of breast
cancer
• Many trials require tissue prescreening with a
goal of trying to deliver personalized medicine

19. Common Questions

20. Will I get a placebo?

21. • No-- phase I trials do not administer placebos

22. How often will I need to come in
for visits?

23. • Each trial is different, but generally most
phase I studies have at least weekly visits for
the first cycle (3-4 weeks) then fewer visits
thereafter

24. How will you know if the drug is
working?

25. • Frequency of imaging is dependent on the
study, but generally every 6-9 weeks

26. Why should I do a clinical trial?

27. Weigh Pros and Cons
Pros:
• If a new treatment is proven to work and you are receiving it,
you may be among the first to benefit
• You can expand the number of treatment options you have
• You have a chance to help others and improve cancer care
Cons:
• New treatments may have side effects that doctors do not
expect
• Phase I trials often involve frequent visits during the first cycle
• Even if a new treatment has benefits, it may not work for you

28. Will my insurance pay for me to
participate in the trial?

29. • Generally, almost all insurance companies pay
for patients to participate in phase I clinical
trials
• Anything that is for research purposes (ie.
research blood, biopsies) is provided by
research
• Experimental medication is provided