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

Plain English Summary

De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA) is a Phase 3 clinical trial sponsored by NRG Oncology studying Stage I Breast Cancer. This trial tests if a shorter course of radiation therapy, combined with hormone therapy, is as effective as standard radiation plus hormone therapy in preventing breast cancer from returning in the same breast. It is for women with early-stage (Stage I), hormone-sensitive, HER2-negative breast cancer who have had surgery to remove the tumor and have a low score on the Oncotype DX test (18 or less). Participation involves being randomly assigned to receive either standard radiation plus hormone therapy or a de-escalated radiation approach plus hormone therapy. Alternatives include standard radiation therapy with hormone therapy, or in some cases, mastectomy if radiation is not preferred or suitable. The trial aims to enroll 1670 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have Stage I breast cancer that is hormone-sensitive, HER2-negative, and has a low Oncotype Recurrence Score (18 or less). You must have had surgery (lumpectomy) to remove the tumor with clear margins and have had your lymph nodes checked. You cannot join if you have metastatic disease, larger tumors (T2-T4), positive lymph nodes, or have had a mastectomy. You must be able to take hormone therapy for at least 5 years and have a good general health status (ECOG 0 or 1). This trial is studying Stage I Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures whether the cancer returns in the same breast, indicating if the de-escalated radiation approach is as effective as the standard approach in preventing recurrence. The specific primary outcome measures are: Time to invasive or noninvasive IBTR. (5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to reduce the side effects of radiation therapy for a specific group of early-stage breast cancer patients, potentially improving quality of life without compromising cancer control. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Stage I Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial addresses a significant market for early-stage breast cancer treatments by seeking to optimize care for patients with low-risk disease, potentially setting a new standard of care and reduci Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1670 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific type of radiation therapy you might receive and the potential side effects. Understand that you will be randomly assigned to one of two treatment groups, and participation will involve regular follow-up appointments for several years. Be prepared to take hormone therapy for at least five years, which may have its own side effects. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 1,670 participants

Interventions

• OTHER: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane) — Post lumpectomy radiation therapy will be external beam radiation to either the whole breast + boost, partial breast irradiation, or Accelerated Partial Breast Irradiation that must begin within 12 weeks of the last breast cancer surgery(including re-excision of margins). Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the ins
• DRUG: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane) — Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s).

Primary Outcomes

• Time to invasive or noninvasive IBTR. (5 years)

Secondary Outcomes

• Percent of women with an intact index breast at report of the primary endpoint inclusive of salvage second breast conservation procedures. (Through study completion, an average of 15 years.)
• Time from randomization to the first occurrence of invasive ipsilateral breast tumor recurrence. (5 years)
• Time from randomization to diagnosis of a local, regional or distant recurrence as a first cancer event. (5 years)
• Time from randomization to the first distant cancer event (either a recurrence or a secondary primary cancer). (5 years)
• Time from randomization to any death. (5 years)

Full Eligibility Criteria

Inclusion Criteria:

* • The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry/Step 1 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) or patients at Canadian provinces or approved international sites where Oncotype DX Recurrence Score testing would not be covered, who do not already have an Oncotype DX Recurrence Score at pre-entry/Step 1, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory. Tumor size sample must be greater than or equal to 0.2 cm for analysis.

    \*\*\* The Oncotype RS can be run on the biopsy core or surgical specimen. The patient cannot have initiated endocrine therapy prior to tissue collection.
  * An Oncotype RS is required for eligibility, however, for a patient whose tumor has already had a MammaPrint test completed as part of usual care when being considered for enrollment and is in the binary "Low" category will meet this eligibility criteria and an Oncotype RS does not need to be performed.
  * 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 pre-entry/Step 1. For study purposes, postmenopausal is defined as:
  * Age 56 or older with no spontaneous menses for at least 12 months prior to pre-entry/Step 1; or a documented hysterectomy; or
  * Age 55 or younger with no spontaneous menses for at least 12 months prior to pre-entry/Step 1 (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 pre-entry/Step 1 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 pre-entry/Step 1. 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:

* • Definitive clinical or radiologic evidence of metastatic disease.

  * pT1 mi and pT2 - pT4 tumors including inflammatory breast cancer.
  * Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
  * Patient had a mastectomy.
  * Palpable or radiographically suspicious ipsilateral or contralateral axillary, 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.
  * Non-epithelial breast malignancies such as sarcoma or lymphoma.
  * 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.)
  * Paget's disease of the nipple.
  * Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous i

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• University of South Alabama Mitchell Cancer Institute, Mobile, Alabama, United States
• Kingman Regional Medical Center, Kingman, Arizona, United States
• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Kaiser Permanente-Anaheim, Anaheim, California, United States
• Kaiser Permanente-Deer Valley Medical Center, Antioch, California, United States
• Mission Hope Medical Oncology - Arroyo Grande, Arroyo Grande, California, United States
• PCR Oncology, Arroyo Grande, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Stage I Breast Cancer
• Hormone-Sensitive Breast Cancer
• HER2-Negative Breast Cancer
• ER-Positive Breast Cancer
• PR-Positive Breast Cancer
• Oncotype DX Recurrence Score Low
• Breast Conservation Therapy
• Adjuvant Therapy
• Radiation Oncology

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