Breast Cancer
NRG-BR009: A Phase III Adjuvant Trial Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients with pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score
Description
This is a Phase III adjuvant trial evaluating the addition of adjuvant chemotherapy to ovarian function suppression plus endocrine therapy in premenopausal patients with Pn0-1, ER-Positive/HER2-Negative Breast Cancer and Oncotype Recurrence Score < 25.
Inclusion Notes
For a full description of this trial, please go to the listing on www.clinicaltrials.gov
Eligibility Criteria
A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
The patient or a legally authorized representative must provide study-specific informed NRG-BR009 21 Version Date: July 27, 2023 consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
Female patients must be ≥ 18 years of age.
Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
Age 50 years or under with spontaneous menses within 12 months; or
Age > 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
The patient must have an ECOG performance status of ≤ 2 (or Karnofsky ≥ 60%).
Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
Patients may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
For patients who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS are eligible without additional resection.)
For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT of the chest wall will be administered.)
Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
Oncotype DX RS requirements*:
If node-negative:
Oncotype DX RS must be RS 21-25, or
Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as: low histologic grade with primary tumor size > 3 cm, intermediate histologic grade with primary tumor size > 2 cm, or high histologic grade with primary tumor size > 1 cm.
If 1-3 nodes involved:
Oncotype DX RS must be < 26.
* Patients with a “Low Risk” or “MP1” MammaPrint result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
The tumor must be ER and/or PgR-positive by current ASCO/CAP guidelines based on local testing results. Patients with ≥ 1% ER and/or PgR staining by IHC will be classified as positive.
The tumor must be HER2-negative by current ASCO/CAP guidelines based on local testing results.
The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
Short course of endocrine therapy of less than 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. This would include prior cancers treated with curative intent.
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Radiation therapy should be used according to standard guidelines; the intended radiation therapy should be declared prior to pre-entry.
Start Date
Wednesday, August 21, 2024
Principal / Contact Name
Alison Spellman, MD