Shorted Adjuvant Regional Nodal Irradiation for the Treatment of Patients with Lymph Node-Positive and High-Risk Lymph Node Negative Invasive Breast Cancer
This phase II trial compares the side safety, side effects and effectiveness of a shortened radiation treatment to the standard length treatment for patients with lymph node positive and high risk lymph node negative invasive breast cancer. Patients with breast cancer can benefit from regional nodal irradiation (RNI) to help control the disease after a lumpectomy or mastectomy surgery. RNI delivers radiation to regional lymph nodes to kill remaining cancer cells. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may work as well as standard length treatment and have fewer side effects.
Inclusion Criteria
- Histologically confirmed invasive breast cancer (nodal involvement from presumed invasive breast cancer in the setting of occult breast cancer is sufficient to meet this criteria)
- Regional nodal irradiation recommended by treating radiation oncologist
- Negative final surgical margins
- No more than 12 weeks have elapsed since final breast/lymph node surgery for patients treated with surgery alone or neoadjuvant chemotherapy. No more than 12 weeks have elapsed since final cytotoxic chemotherapy for patients who received adjuvant chemotherapy
- Age ≥ 18 years. Because breast cancer is exceedingly rare in patients < 18 years of age, children are excluded from this study
- Patients with a prior or concurrent malignancy are eligible provided that the natural history and treatment of the prior or concurrent malignancy does not interfere with the safety or efficacy assessment of the investigational radiation regimen used in this trial
- Ability to understand and the willingness to sign a written informed consent document
- Concurrent enrollment on other observational, translational, or therapeutic studies is allowed provided there is no direct conflict between the other protocol and the radiation regimen proscribed in this trial
- LOW RISK LUMPECTOMY: For patients treated with upfront surgery, pathologic stage pT0-T4b N0-N3a breast cancer without infraclavicular or internal mammary nodal involvement
- LOW RISK LUMPECTOMY: For patients treated with neoadjuvant chemotherapy, clinical stage cT0-T4b N0-N2a breast cancer
- LOW RISK LUMPECTOMY: Treated with lumpectomy (or axillary surgery only in the case of occult primary breast cancer)
- LOW RISK LUMPECTOMY: No nodal boost recommended by the treating radiation oncologist
- HIGH RISK LUMPECTOMY: Treated with neoadjuvant chemotherapy
- HIGH RISK LUMPECTOMY: Clinical stage cT0-T4b N1-N3a/b/c
- HIGH RISK LUMPECTOMY: Treated with lumpectomy (or axillary surgery only in the case of occult primary breast cancer)
- HIGH RISK LUMPECTOMY: Nodal boost recommended by the treating radiation oncologist
- LOW RISK MASTECTOMY: For patients treated with upfront surgery, pathologic stage T0-T2 N0-N2a
- LOW RISK MASTECTOMY: For patients treated with neoadjuvant chemotherapy, clinical stage T0-T3 N0-N2a
- LOW RISK MASTECTOMY: For patients treated with neoadjuvant chemotherapy, residual cellularity of primary tumor ≤ 20%
- LOW RISK MASTECTOMY: Treated with mastectomy
- LOW RISK MASTECTOMY: Negative surgical margins ≥ 2 mm
- LOW RISK MASTECTOMY: No or only focal lymphovascular space invasion
- LOW RISK MASTECTOMY: Age ≥ 40 years
- LOW RISK MASTECTOMY: Chest wall boost NOT recommended by treating radiation oncologist
- HIGH RISK MASTECTOMY: For patients treated with upfront surgery, pathologic stage T0-T4d N0-N3c
- HIGH RISK MASTECTOMY: For patients treated with neoadjuvant chemotherapy, clinical stage T0-T4d N0-N3c
- HIGH RISK MASTECTOMY: Treated with mastectomy
- HIGH RISK MASTECTOMY: Chest wall boost and/or nodal boost recommended by treating radiation oncologist
- Pregnancy Status (applicable to all cohorts): Therapeutic radiation is known to be teratogenic. As a result, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of radiation treatment. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the radiation therapy course is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception during the radiation treatment course. Pregnancy testing at the time of study enrollment is not required of women who enroll. However, all patients must comply with the Institutional Pregnancy Assessment Policy (# CLN1114) which requires pregnancy testing within 7 days prior to simulation
Exclusion Criteria
- History of therapeutic radiation overlapping with the index breast or nodal basins that require radiation therapy
- History of scleroderma
- Pregnant women are excluded from this study because ionizing radiation has the potential for teratogenic or abortifacient effects
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07076485.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVE:
I. To compare the occurrence of any grade 2 or higher National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity from start of RNI through 18 months follow up by treatment arm for each of the four randomized cohorts (low-risk lumpectomy, low-risk mastectomy, high-risk lumpectomy, high-risk mastectomy).
SECONDARY OBJECTIVES:
I. To compare treatment toxicity, local-regional control, disease-free survival, and overall survival by treatment arm for each of the four randomized cohorts.
II. To compare patient-reported outcomes including cosmetic satisfaction, physical wellbeing, lymphatic function, and financial toxicity by treatment arm for each of the four randomized cohorts.
III. To compare photographic outcome of the treated breast or reconstructed breast by treatment arm for each of the four randomized cohorts.
IV. To evaluate and compare radiation treatment plans by treatment arm for each of the four randomized cohorts, including target coverage, dose to organs at risk, dose homogeneity, and low-dose scatter.
V. To compare biometric data before, during, and after radiation collected by patients’ personal Apple Watches.
OUTLINE: Low risk lumpectomy patients are randomized to arm I or II, high risk lumpectomy patients are randomized to arm III or IV, low risk mastectomy patients are randomized to arm V or VI and high risk mastectomy patient are randomized to arm VII or VIII.
ARM I: Patients receive ultrahypofractionated radiation treatment for 5 sessions in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive modestly hypofractionated radiation treatment for 15 sessions in the absence of disease progression or unacceptable toxicity.
HIGH RISK LUMPECTOMY:
ARM III: Patients receive modestly hypofractionated radiation treatment for 15 sessions in the absence of disease progression or unacceptable toxicity.
ARM IV: Patients receive hypofractionated radiation treatment with a sequential boost for 19-23 sessions in the absence of disease progression or unacceptable toxicity.
LOW RISK MASTECTOMY:
ARM V: Patients receive ultrahypofractionated radiation treatment for 5 sessions in the absence of disease progression or unacceptable toxicity.
ARM VI: Patients receive modestly hypofractionated radiation treatment for 15 sessions in the absence of disease progression or unacceptable toxicity.
HIGH RISK MASTECTOMY:
ARM VII: Patients receive modestly hypofractionated radiation treatment for 15 sessions in the absence of disease progression or unacceptable toxicity.
ARM VIII: Patients receive modestly hypofractionated radiation with a sequential boost treatment for 19-23 sessions in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 6 months, 1.5, 3.5, 5.5 and 10.5 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorBenjamin David Smith
- Primary ID2025-0779
- Secondary IDsNCI-2025-05190
- ClinicalTrials.gov IDNCT07076485