Serum Tumor Marker Directed Disease Monitoring in Patients With Hormone Receptor Positive Her2 Negative Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. To assess whether patients with HER-2 negative, hormone receptor positive, metastatic
breast cancer who are monitored with serum tumor marker directed disease monitoring (STMDDM)
have non-inferior overall survival compared to patients monitored with usual care.

SECONDARY OBJECTIVES:

I. To compare cumulative direct healthcare costs through 48 weeks among patients monitored
with STMDDM versus those monitored with usual care in this patient population.

II. To assess whether the patient-reported outcomes (PROs) of anxiety and quality of life
(QOL) are different among patients who are monitored with STMDDM compared with patients who
are monitored with usual care in this patient population.

TERTIARY OBJECTIVES:

I. To assess modality and frequency of disease monitoring testing in the usual care cohort.

II. To assess the association of PROs and patient preferences for disease monitoring testing.

III. To evaluate predictors of physician preferences for disease monitoring testing.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients undergo imaging studies at a minimum frequency of every 12 weeks and continue
with usual care disease monitoring for up to 312 weeks in the absence of disease progression.

ARM II: Patients undergo disease specific serum tumor marker (STM) evaluation every 6 weeks.
Patients with elevated STM, undergo imaging evaluation. Patients continue with STMDDM for up
to 312 weeks in the absence of disease progression.

Inclusion Criteria:

- STEP 1 REGISTRATION

- Patients must have a diagnosis of hormone receptor positive (estrogen receptor
positive [ER+] and/or progesterone receptor positive [PR+]), HER-2 negative,
metastatic (M1) breast cancer and must be receiving or plan to receive first-line
systemic treatment for metastatic disease

- NOTE: Participants are eligible if they have either de-novo metastatic breast
cancer and/or recurrent breast cancer from an earlier stage that is now
metastatic

- Patients must be registered to step 1 between 14 days prior to and 28 days after start
of first-line systemic treatment for metastatic disease

- Patients must have been tested for all of the following breast cancer specific STMs
after diagnosis of metastatic disease and within +/-14 days of initiation of
first-line systemic treatment for metastatic disease:

- CA 15-3

- CA 27.29

- CEA

- At least one of these STMs must have been >= 2 x the institutional upper limit of
normal at this time

- Patients must have systemic radiographic imaging prior to initiation of systemic
therapy for treatment of metastatic breast cancer and prior to step 1 registration
with either:

- A computed tomography (CT) scan of the chest and abdomen with or without CT
pelvis, and with or without bone scan or

- A positron emission tomography (PET) scan with or without CT

- Note: the treating physician can order additional imaging tests at any point
prior to randomization at their discretion

- Patients must be willing to obtain disease monitoring (imaging and/or serum tumor
markers) at their current center for the duration of the study intervention (312 weeks
after step 2 randomization)

- Patients with known cirrhosis, untreated B12 deficiency, thalassemia, or sickle cell
anemia are not eligible as these could cause falsely elevated STM levels

- Patients with known brain metastases are not eligible as they may require regular
radiographic monitoring to assess treatment response

- Patients must not be currently enrolled or plan to participate in a first-line
treatment trial for metastatic breast cancer with a defined monitoring schedule

- Patients who are able to complete questionnaires in English or Spanish must
participate in patient-reported outcome (PRO) assessments

- Patients must not be pregnant due to the potential harm to the fetus from radiation
exposure from radiographic imaging

- Except for breast cancer (and previous history of breast cancer), no other prior
malignancy is allowed except for adequately treated basal (or squamous cell) skin
cancer, in situ cervical cancer or other cancer for which the patient has been disease
free for five years

- Patients must not have received prior systemic therapy for metastatic breast cancer,
except for their current treatment regimen initiated no more than 28 days prior to
registration

- Patients must have decision making capacity and be able to provide informed consent

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines; use of legally-authorized representative is not permissible for this study

- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system

- STEP 2 RANDOMIZATION

- Patients must be tested for all of the following breast cancer specific STMs between
56 and 112 days after initiation of first-line systemic therapy for metastatic
disease:

- CA 15-3

- CA 27.29

- CEA

- At least one of the STMs that was previously elevated must have decreased from the
assessment at step 1 by >= 25% at this time

- Patients must not have known progression since registration to step 1

- Patients must be registered to step 2 randomization between 56 days and 112 days after
the initiation of first-line systemic therapy for metastatic disease; patients must
have been eligible for step 1 in order to be eligible for step 2 randomization

- Baseline questionnaires must be completed within 28 days prior to step 2
randomization; (Note: Those patients who cannot complete the PRO questionnaires in
English or Spanish can be registered to step 2 without contributing to PRO research)