Trial Information

Program for the Assessment of Clinical Cancer Tests (PACCT-1): Trial Assigning Individualized Options for Treatment: The TAILORx Trial

PRIMARY OBJECTIVES:

I. To determine whether adjuvant hormonal therapy is not inferior to adjuvant chemohormonal
in women whose tumors meet established clinical guidelines for adjuvant chemotherapy and
fall in the "primary study group" category (Oncotype DX Recurrence Score 11-25).

II. To create a tissue and specimen bank for patients enrolled in this trial, including
formalin fixed paraffin embedded tumor specimens, tissue microarrays, plasma, and DNA
obtained from peripheral blood.

SECONDARY OBJECTIVES:

I. To determine whether adjuvant hormonal therapy is sufficient treatment (i.e. 10 year
distant disease-free survival of at least 95%) for women whose tumors meet established
clinical guidelines for adjuvant chemotherapy and who fall into the "Secondary Study
Group-1" category (Oncotype DX Recurrence Score =< 10).

II. To compare the outcomes projected at 10 years by Adjuvant! (with outcomes projected
using classical pathologic information including tumor size, hormone receptor status, and
histologic grade) with those made by the Genomic Health Oncotype DX test. Classical
pathologic information and outcome results will also be used to create and refine models
that would use classical information instead of or in combination with genomic tests.

III. To estimate failure rates as a function of RS separately in the chemotherapy (arms C,
D) and no chemotherapy (arms A, B) groups. The purpose of the analysis is to develop more
precise estimates of the relationship between recurrence score and chemotherapy treatment
effect, if any, at the upper range of the RS 11 - 25 group.

IV. RS gene groups (proliferation gene group, HER2 gene group, ER gene group, invasion gene
group, and other genes).

TERTIARY OBJECTIVES:

I. To evaluate the effects of chemotherapy and hormonal therapy vs hormonal therapy alone on
perceived cognitive impairment, fatigue, fear of recurrence among pre-menopausal patients,
endocrine symptoms and sexual dysfunction, and overall health-related quality of life
(HRQL).

II. To determine whether perceived cognitive impairment, fatigue, fear of recurrence,
endocrine symptoms, and overall HRQL are similar for patients receiving chemotherapy plus
hormonal therapy in secondary study group 2 as for those in the primary study group (arm D
vs C).

III. To determine whether perceived cognitive impairment, fatigue, fear of recurrence,
endocrine symptoms, and overall HRQL are similar for patients receiving hormonal therapy
alone in secondary study group 1 as for those in the primary study group (arms A vs B).

IV. To determine whether age will be inversely associated with a fear of recurrence,
independent of treatment assignment.

V. Among participants receiving hormonal treatment alone on arm A and arm B, to determine
whether ODRS will be inversely correlated with fear of recurrence.

VI. To create a biospecimen repository including plasma, serum and CellSearch cassettes
containing circulating tumor cells (CTC) for evaluating determinants of late relapse,
including candidate biomarkers reflecting occult tumor burden (e.g., CTCs and plasma tumor
DNA) and host factors (e.g., estrogen, insulin-IGF axis, inflammation, etc).

VII. To create a biorepository of metastatic tumor samples in patients who have had a late
relapse.

VIII. To determine body mass index (BMI) and comorbidity burden in patients with operable
breast cancer five or more years after diagnosis.

IX. To determine whether there is a relationship between late relapse and BMI at diagnosis
and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic
biomarkers are associated with early and late recurrence.

OUTLINE: This is a multicenter, partially randomized study. Patients are assigned to 1 of 3
treatment groups based on their risk of distant recurrence determined by Oncotype DX Breast
Cancer Assay.

GROUP 1 (SECONDARY STUDY GROUP 1; ONCOTYPE DX RECURRENCE SCORE [ODRS] < 11): Patients
receive standard hormonal therapy (e.g., oral tamoxifen alone, oral aromatase inhibitor
[e.g., anastrozole, letrozole, or exemestane] alone, or oral tamoxifen followed by oral
aromatase inhibitor) at the discretion of the treating physician for 5 or 10 years.

GROUP 2 (PRIMARY STUDY GROUP; ODRS 11-25): Patients are stratified according to tumor size
(≤ 2.0 cm vs ≥ 2.1 cm), menopausal status (postmenopausal vs premenopausal vs
perimenopausal), planned chemotherapy (taxane-containing [i.e., paclitaxel, docetaxel] vs
nontaxane-containing), planned radiotherapy (whole breast with no boost planned vs whole
breast with boost planned vs partial breast irradiation planned vs no planned radiation
therapy [for patients who have had a mastectomy]) and Oncotype DX Recurrence Score (11-15 vs
16-20 vs 21-25). Patients are then randomized to receive either hormonal therapy alone or
combination chemotherapy and hormonal therapy.

ARM I (EXPERIMENTAL): Patients receive hormonal therapy as in group 1 at the discretion of
the treating physician.

ARM II (STANDARD): Patients receive standard combination chemotherapy at the discretion of
the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive
hormonal therapy as in group 1 at the discretion of the treating physician.

GROUP 3 (SECONDARY STUDY GROUP 2; ODRS > 25): Patients receive combination chemotherapy as
in group 2, arm II followed by hormonal therapy as in group 1.

Patients in all groups who have had breast-conservation surgery are also treated with
radiotherapy. Radiotherapy should begin within 4 weeks of registration for patients
receiving hormonal therapy alone or within 8 weeks after completion of chemotherapy.
Patients participating in NSABP and/or RTOG partial irradiation trial(s) may receive partial
breast radiation.

Tissue obtained at surgery (performed prior to study entry) is examined by the Oncotype DX
Recurrence Score Assay and other assays to correlate response with various biomarkers.
Patients may complete quality-of-life assessments at baseline and at 3, 6, 12, 24, and 36
months.

After completion of study treatment, patients are followed up periodically for up to 20
years.