Trial Information

Phase II Study of PET Guided Neoadjuvant Chemotherapy (NAC) and Oncotype Guided Hormonal Therapy of Breast Cancer: CCAM 11-01

OBJECTIVES:

Primary

- To evaluate a novel neoadjuvant regimen by using the MD Anderson residual cancer burden
score in treating patients with invasive breast cancer.

Secondary

- To prospectively evaluate the utility of the PET scan to guide the neoadjuvant
treatment in these patients.

- To prospectively evaluate the Oncotype test as a tool to stratify
ER-positive/HER2-negative patients after treatment.

- To evaluate the clinical anti-tumor activity of neoadjuvant hormonal therapy in
ER-positive/HER2-negative patients.

- To evaluate the prognostic factors associated with pathological response as measured by
the residual cancer burden tool.

OUTLINE: Patients are divided according to receptor status: Her2+ (includes ER+, ER-, and
PR+) vs ER- (includes triple negative and ER/PR/Her2-) vs ER+ (includes ER+/PR+/Her2- and
ER+/PR-/Her2-). Patients are assigned to 1 of 3 treatment groups.

All patients, regardless of receptor status, receive docetaxel IV over 60 minutes,
epirubicin hydrochloride IV over 15-20 minutes, and cyclophosphamide IV over 20-30 minutes
on day 1 (TEC regimen). For ER+/Her2- patients, subsequent therapy after TEC course 1
depends on Oncotype score. For other patients, treatment with TEC repeats every 21 days for
up to 4 courses in the absence of disease progression or unacceptable toxicity.

- Her2+ (includes ER+, ER-, and PR+): Patients are evaluated after 4 courses of TEC
therapy. Patients who achieve complete remission (CR) or partial remission (PR) receive
docetaxel IV over 60 minutes and trastuzumab IV over 60 minutes on day 1. Treatment
repeats every 21 days for 4 courses, followed by surgery with sentinel node biopsy
and/or axillary dissection. Patients with progressive disease (PD) or stable disease
(SD) after TEC receive vinorelbine tartrate IV over 60 minutes on days 1 and 8;
trastuzumab IV over 60 minutes on day 1; and oral capecitabine twice daily on days 1-14
(NTX regimen). Treatment with NTX repeats every 21 days for 4 courses, followed by
surgery with sentinel node biopsy and/or axillary dissection. After surgery, patients
receive radiotherapy (when indicated) and maintenance trastuzumab for 1 year.
ER-positive or PR-positive patients also receive hormonal therapy for 5 years.

- ER- ( includes triple negative or ER-/PR+/Her2-): Patients are evaluated after 4
courses of TEC therapy. Patients who achieve CR receive 4 more courses of TEC and
undergo surgery with sentinel node biopsy and/or axillary dissection. Patients who
achieve PR or stable disease (SD) receive vinorelbine tartrate IV over 60 minutes on
days 1 and 8; bevacizumab IV over 90 minutes on days 1 and 8; and oral capecitabine
twice daily on days 1-14 (NAX regimen). Treatment with NAX repeats every 21 days for 4
courses in the absence of disease progression or toxicity. Approximately 28 days after
the last dose of bevacizumab, patients proceed to surgery with sentinel node biopsy,
and/or axillary dissection.

- ER+ (includes ER+/PR+/Her2- or ER+/PR-/Her2-) : Patients undergo a PET scan 2 weeks
after finishing 1 course of TEC therapy. If the drop of measured standardized uptake
value (SUV) of primary tumor is > 5%, patients receive 3 additional courses of TEC
therapy followed by additional therapy depends on the the Oncotype results. If the drop
of measured SUV of primary tumor is ≤ 5% (after 1 course of TEC therapy), patients
receive additional therapy depends on the Oncotype results.

- Low Oncotype recurrence score: Patients receive hormonal therapy for 6 months,
followed by surgery.

- Intermediate or high Oncotype recurrence score: Patients receive NAX chemotherapy
for 4 courses. Approximately 6 weeks after completion of course 4, patients
undergo surgery.

All patients in this group receive hormonal therapy for a total of 5 years (counting from
the first dose).

After completion of study treatment, patients are followed up periodically.