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A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and Her2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: a Clinical Trial Rx or Positive Node, Endocrine Responsive Breast Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Thank you

Trial Information

A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and Her2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: a Clinical Trial Rx or Positive Node, Endocrine Responsive Breast Cancer


PRIMARY OBJECTIVES:

I. To determine the effect of endocrine therapy with versus without chemotherapy in patients
with node-positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype DX.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS), distant disease-free survival (DDFS), and local
disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
II. To compare the toxicity across the treatment arms. III. To perform other assays or tests
(in particular the PAM50 risk of relapse score) as they are developed and validated that
measure potential benefit of chemotherapy and compare them to Oncotype DX.

IV. To determine the impact of management with Oncotype DX on patient-reported anxiety
(co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after
disclosure of test results, and during the randomized trial.

V. To determine the impact of Oncotype DX on the initial management cost of node-positive,
HR-positive, HER2-negative breast cancer.

VI. To compare patient-reported utilities (e.g., QOL) for those randomized to chemotherapy
versus no chemotherapy.

VII. To estimate the cost-effectiveness of management with Oncotype DX vs usual care using
modeling and DFS information from the trial.

VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and
LDFI of patients randomized to chemotherapy versus no chemotherapy.

IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on
patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).

X. To determine the impact of management with Oncotype DX on patient-reported decision
conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to
screening, after disclosure of test results, and during the randomized trial (secondary HRQL
outcomes).

OUTLINE: This is a multicenter study. Patients are stratified according to Recurrence Score
(0-13 vs 14-25), menopausal status (pre-menopausal vs post-menopausal), and type of nodal
dissection (axillary lymph node dissection [with or without sentinel node mapping] vs
sentinel node biopsy without axillary lymph node dissection). Patients are randomized to 1
of 2 treatment arms.

ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or
physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy
comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or
exemestane), or both for 5-10 years in the absence of disease progression or unacceptable
toxicity.

ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate,
an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in
the absence of disease progression or unacceptable toxicity.

Patients may complete health-related quality-of-life (QOL) questionnaires at baseline and
periodically during study. Information on Medicare and/or insurance coverage and on health
coverage decisions may also be collected periodically.

After completion of study therapy, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then yearly for at least 15 years.


Inclusion Criteria:



- Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes)
invasive breast carcinoma with positive estrogen and/or progesterone receptor status,
and negative HER-2, as determined by IHC or gene amplification evaluation (e.g. FISH,
CISH, etc.); estrogen and progesterone receptor positivity must be assessed according
to ASCO/CAP guidelines as either ER or PR >= 1% positive nuclear staining; if HER2
IHC is 2+, an evaluation for gene amplification must be performed and must not be
amplified, but otherwise gene amplification evaluation is not required if IHC is 0 or
1+ by institutional standards

- Patients must not have inflammatory breast cancer and must not have metastatic
disease; patients with a prior diagnosis of DCIS are eligible if they received
mastectomy alone (no therapeutic radiation, intraoperative radiation, or endocrine
therapy); radiation in the opposite breast is acceptable

- Must have had breast-conserving surgery with planned radiotherapy or total mastectomy
(with or without planned post mastectomy radiation) with clear margins within the
past 28-84 days

- Menopausal status: pre- or post-menopausal

- Zubrod performance status 0-2

- Not pregnant or nursing

- Fertile patients must use an effective non-hormonal contraception method while on
treatment and for ≥ 3 months after completion of protocol treatment

- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer; in situ cervical cancer; adequately treated stage 0, I, or II cancer from
which the patient is currently in complete remission; or any other cancer from which
the patient has been disease-free for the past 5 years

- LVEF ≥ 50% if an anthracycline-based regimen is planned

- Patients randomized to chemotherapy may also co-enroll in Phase III trials that
compare chemotherapies

- No prior chemotherapy or endocrine therapy for breast cancer

- No prior preventive tamoxifen or raloxifene

- No prior therapeutic breast radiotherapy

- Not requiring concurrent chronic treatment with systemic steroids or other
immunosuppressive agents

- Patients randomized to either arm may also co-enroll in Phase III trials that compare
local therapies or compare systemic therapies (not including chemotherapy)

- Patients with multifocal, multicentric and synchronous bilateral breast cancers are
allowed

- Multifocal disease is defined as more than one invasive cancer < 2 cm from the
largest lesion within the same breast quadrant; (NOTE: The Oncotype DX testing
must be completed on the largest lesion)

- Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the
largest lesion within the same breast quadrant or more than one lesion in
different quadrants; (NOTE: Oncotype DX testing should be completed on all
tumors and the determination for eligibility should be made on the highest
recurrence score)

- Synchronous bilateral disease is defined as invasive breast cancer with positive
lymph nodes (axillary or intramammary) in at least one breast, diagnosed within
30 days of each other; (NOTE: The Oncotype DX testing should be completed on
both tumors and the tumor with the highest recurrence score should be used)

- Patients must be able to receive taxane and/or anthracycline based chemotherapy

- The Quality of Life and Economic Substudy is permanently closed to accrual effective
12/1/12; patients who are able to complete a questionnaire in English must be offered
the opportunity to participate in the Quality of Life and Economic Substudy. (The
Quality of Life and Economic Substudy is available to U.S. INSTITUTIONS ONLY);
patients who are not able to complete a questionnaire in English are registered to
S1007 without participating in the Quality of Life and Economic Substudy

- Patients who consent to participate in the Quality of Life and Economic Substudy
and who do not yet know the results of their Oncotype DX screening must agree to
complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment
between 14 days prior to and 7 days after Step 1 Registration

- Patients who consent to participate in the Quality of Life and Economic Substudy
and who do already know their Oncotype DX Recurrence Score (and it is 25 or
less) will proceed to Step 2 Registration without completing the S1007
Health-Related Quality of Life Questionnaire Enrollment Form (but will complete
the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form)

- Patients or their legally authorized representative 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; for Step 1 registration of
patients who have not yet submitted specimens for the Oncotype DX Breast Cancer
Assay, the appropriate consent form is the Step 1 Consent Form; for both Step 1 and
Step 2 registration of patients whose Recurrence Score is already known and is 25 or
less, the appropriate consent form is the Step 2 Consent Form

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Invasive disease-free survival (DFS) of women with node-positive breast cancer treated with endocrine therapy with vs without chemotherapy

Outcome Description:

Defined as the time from the second registration (randomization) to local, regional, or distant recurrence, new invasive primary, or death due to any cause. The STEEP definition of invasive disease-free survival (IDFS) is used, although it is referred to here by the more common acronym DFS. Survival times are censored at time of last follow-up for individuals who did not have any event meeting the above definition.

Outcome Time Frame:

Up to 15 years

Safety Issue:

No

Principal Investigator

Ana Maria Gonzalez-Angulo

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02623

NCT ID:

NCT01272037

Start Date:

January 2011

Completion Date:

Related Keywords:

  • Estrogen Receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Breast Neoplasms

Name

Location

Aspirus Regional Cancer CenterWausau, Wisconsin  54401