A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)

  • STATUS
    Recruiting
  • End date
    Jul 16, 2041
  • participants needed
    1670
  • sponsor
    NRG Oncology
Updated on 16 September 2022
Investigator
Director Department of Regulatory Affairs
Primary Contact
Poudre Valley Hospital (1.6 mi away) Contact
+411 other location

Summary

This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.

Description

Breast conservation therapy for early stage breast cancer has been an important achievement of oncology practice in the last half century and breast radiotherapy (RT) has been essential in its development. Several seminal randomized clinical trials conducted in the 1980's era demonstrated that breast radiotherapy following lumpectomy yielded overall survival outcomes equivalent to mastectomy for treatment of early stage invasive breast cancer leading to the National Institute of Health (NIH) Consensus Conference statement in 1991 supporting breast conservation treatment.This established lumpectomy with RT as an alternative to mastectomy and subsequently the rate of breast conservation for eligible breast cancer patients rose steadily. Shortly thereafter, investigators recognized that the toxicity, patient burden, and geographic barriers associated with the protracted treatment course for breast RT was a potential barrier to breast conservation utilization. Numerous phase III clinical trials were conducted randomizing women post lumpectomy to RT vs. observation aimed at identifying which cases did not derive a significant RT benefit. No such subsets of breast cancer patients were consistently identified, thereby solidifying the standard that breast conservation required both lumpectomy and RT. Two meta-analyses by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) in 2005 and 2011 further reinforced the value of breast RT post lumpectomy by examining the relationship of local recurrence and breast cancer mortality relative to the use of breast RT post lumpectomy. In each analysis, it found for axillary node negative breast cancer patients undergoing breast conservation a small but consistent increase in breast cancer mortality when breast radiotherapy was omitted. As a result, breast RT after lumpectomy has become an established paradigm for breast conservation for early stage breast cancer and is recommended by the NCCN 2018 guidelines (as it has for nearly two decades) that are commonly used today by clinicians and health systems alike. The landscape of early stage breast cancer has changed dramatically over the past three decades since the establishment of breast conservation. Widespread screening with mammography has led to the diagnosis of smaller and earlier stage disease. All breast cancers are now routinely characterized by their hormone sensitivity based on the presence of estrogen and progesterone receptors on tumor cells within the biopsy or surgical specimen and presence of HER2 (human epidermal growth factor receptor 2) which has provided an additional means of stratifying breast cancer into distinct prognostic groups. Small, node negative invasive breast cancer that is hormone sensitive (HS) and HER2-negative has a lower overall recurrence rate (local, regional, and distant) than breast cancers characterized by more adverse clinical pathologic features. However, other than in a smaller subset of women greater than 70 years old, clinical trials in this HS population still demonstrated unacceptable local recurrence risks long term after lumpectomy alone emphasizing that clinical and pathologic features are insufficient for consistently identifying when RT can safely be omitted.

Details
Condition Stage I Breast Cancer
Treatment Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane), Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)
Clinical Study IdentifierNCT04852887
SponsorNRG Oncology
Last Modified on16 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information
The patient must have an ECOG performance status of 0 or 1
The patient must have undergone a lumpectomy and 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. (Patients with margins positive for LCIS are eligible without additional resection.)
The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection)
The following staging criteria must be met postoperatively according to AJCC 8th edition criteria: By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm)
By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging
of pN0(i+) or pN0(mol+) are NOT eligible.)
Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or
resected specimen
For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not
already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained
blocks or slides) must be sent to the Genomic Health centralized laboratory
The tumor must have been determined to be ER and/or PgR positive assessed by current
ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater
than or equal to 1% ER or PgR staining by IHC are considered positive
The tumor must have been determined to be HER2-negative by current ASCO/CAP
guidelines
Patients may be premenopausal or postmenopausal at the time of study entry. For study
purposes, postmenopausal is defined as: Age 56 or older with no spontaneous menses for
at least 12 months prior to study entry; or a documented hysterectomy; or Age 55 or
younger with no spontaneous menses for at least 12 months prior to study entry (e.g
spontaneous or secondary to hysterectomy) and with a documented estradiol level in the
postmenopausal range according to local institutional/laboratory standard; or
Documented bilateral oophorectomy
The interval between the last surgery for breast cancer (including re-excision of
margins) and study entry must be no more than 70 days
The patient must have recovered from surgery with the incision completely healed and
no signs of infection
Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients
on effective anti-retroviral therapy with undetectable viral load within 6 months are
eligible for this trial. Patients must be intending to take endocrine therapy for a
minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of
endocrine therapy is at the treating physician's discretion

Exclusion Criteria

pT2 - pT4 tumors including inflammatory breast cancer
Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease
Patient had a mastectomy
Non-epithelial breast malignancies such as sarcoma or lymphoma
Paget's disease of the nipple
Treatment plan that includes regional nodal irradiation
• Definitive clinical or radiologic evidence of metastatic disease
Palpable or radiographically suspicious ipsilateral or contralateral axillary
Prior breast or thoracic RT for any condition
supraclavicular, infraclavicular, or internal mammary nodes, unless there is
histologic confirmation that these nodes are negative for tumor
Suspicious microcalcifications, densities, or palpable abnormalities (in the
ipsilateral or contralateral breast) unless biopsied and found to be benign
Use of any investigational product within 30 days prior to study entry
Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant
or separated by 4 or more centimeters. (Patients with multifocal carcinoma are
eligible.)
Any history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or
previous ipsilateral LCIS are eligible.)
Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients
with synchronous and/or previous contralateral LCIS are eligible.)
Surgical margins that cannot be microscopically assessed or are positive at
pathologic evaluation. (If surgical margins are rendered free of disease by re-
excision, the patient is eligible.)
Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine
therapy administered for the currently diagnosed breast cancer prior to study
entry
(Short course endocrine therapy of less than 6 weeks duration is acceptable post core
biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and
is less than or equal to 18.)
History of non-breast malignancies (except for in situ cancers treated only by local
excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior
to study entry
Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or
other selective estrogen receptor modulators (SERMs), either for osteoporosis or
breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is
acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is
assessed on the biopsy core and is less than or equal to 18.)
Patients intending to continue on oral, transdermal, or subdermal estrogen replacement
(including all estrogen only and estrogen-progesterone formulas) are not eligible
Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior
to registration are eligible
Active collagen vascular disease, specifically dermatomyositis with a CPK level above
normal or with an active skin rash, systemic lupus erythematosis, or scleroderma
Pregnancy or lactation at the time of study entry or intention to become pregnant
during treatment. (Note: Pregnancy testing according to institutional standards for
women of childbearing potential must be performed within 2 weeks prior to study
entry.)
Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of study therapy or that may affect the interpretation of the
results or render the patient at high risk from treatment complications
Psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the patient from meeting the study requirements or
interfere with interpretation of study results
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