Comparing Hypofractionated versus Conventionally Fractionated Radiation Therapy Before Mastectomy with Breast Reconstructive Surgery for the Treatment of Breast Cancer
This phase III trial compares the effect of hypofractionated versus conventionally fractionated radiation therapy (RT) before breast tissue removal (mastectomy) with reconstructive surgery in treating patients with breast cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Conventionally fractionated radiation therapy delivers multiple doses of radiation spread over several treatment sessions. Receiving hypofractionated radiation therapy before mastectomy may improve cosmetic outcomes of breast reconstructive surgery.
Inclusion Criteria
- Age 18 years or older
- Histologic diagnosis of invasive breast cancer (cytologic or histologic confirmation of nodal metastasis is sufficient to establish this eligibility criteria)
- Clinical and/or pathologic stage T3-T4c OR N1-N3; for the inflammatory breast cancer (IBC) pilot cohort only, the stage requirement is T4d, any N, M1
- Mastectomy is the planned oncologic surgery but has not yet been performed at the time of protocol enrollment
- Autologous (i.e. tissue-based) reconstruction is planned with either a free or rotational flap
- For patients with human epidermal growth factor receptor 2 (HER2) positive, non-IBC breast cancer treated with neoadjuvant chemotherapy, one of the following criteria must be met: * Residual invasive disease should be documented in either the breast or a regional nodal metastasis after neoadjuvant chemotherapy. This specific eligibility criteria can be satisfied by the post-chemotherapy standard of care breast biopsy. For this matter, the patient may be enrolled on the trial prior to biopsy. If the biopsy does not show residual invasive disease, then the patient will not proceed with protocol-directed therapy, and will be removed and replaced from the study * Medical oncologist has documented a discussion in the chart about potential risks of proceeding with PreMRT with regard to impact on adjuvant systemic therapy decisions and the patient has opted to proceed with trial enrollment
- For T4d pilot cohort patients, post-chemotherapy, pre-radiation ultrasound must demonstrate at least partial response in the breast and regional lymph nodes and no suspicious infraclavicular, internal mammary, and supraclavicular lymph nodes
- Ability to provide written informed consent in accordance with institutional policies
Exclusion Criteria
- Patients undergoing treatment for recurrent breast cancer in the index breast or lymph nodes
- History of therapeutic irradiation to the breast, lower neck, mediastinum or other area(s) that will overlap with the affected breast
- Presence of active scleroderma
- Patients who are pregnant
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05774678.
Locations matching your search criteria
United States
Texas
Conroe
Houston
League City
Sugar Land
PRIMARY OBJECTIVES:
I. To compare BREAST-Q satisfaction with breasts 18 months after reconstructive surgery for patients randomized to hypofractionated pre-mastectomy radiation therapy (HF-PreMRT) versus conventionally fractionated pre-mastectomy radiation therapy (CF-PreMRT).
SECONDARY OBJECTIVES:
I. To compare oncologic outcomes following HF-PreMRT versus CF-PreMRT, including residual cancer burden, local-regional control, disease-free survival, and overall survival.
II. To compare surgical outcomes following HF-PreMRT versus CF-PreMRT, including surgical complications, flap loss, difficulty of reconstructive surgery, number of reoperations, and aesthetic outcomes including photographic assessment of the reconstructed breast.
III. To compare radiation outcomes following HF-PreMRT versus CF-PreMRT, including acute and late toxicities and fibrosis.
IV. To compare health services research outcomes following HF-PreMRT versus CF-PreMRT, including financial toxicity, work productivity and disability, total cost of care, complication-related cost of care, and health utility.
V. To compare patient-reported quality of life and toxicities following HF-PreMRT versus CF-PreMRT.
VI. To compare patient-reported quality of life and toxicities following HF-PreMRT versus CF-PreMRT.
VII. To evaluate associations between the radiation treatment plan parameters and surgical, radiation, health services, and patient-reported outcomes.
VIII. To evaluate nanomechanical properties of the breast cancer before and after radiation and their association with oncologic outcomes.
IX. To evaluate nanomechanical properties of the breast normal tissue after radiation and their association with surgical and radiation outcomes.
X. To evaluate the association of germline polymorphisms, including the pro-fibrotic cytokine transforming growth factor-beta (TGF-beta), with circulating serum TGF- levels during and after radiation and toxicities of radiation and reconstruction, particularly fibrotic complications.
XI. To characterize pre- and post-radiation tumor and nodal tissue by single cell sequencing, whole genome, whole exome, and targeted sequencing, and digital spatial profiling for immune landscape, radiation resistance signatures, microenvironmental and tumor genome profiles and correlate radiation induced changes to tumor and patient characteristics and residual cancer burden.
XII. To characterize pre- and post-radiation tumor and nodal tissue by single cell sequencing, whole genome, whole exome, and targeted sequencing, and digital spatial profiling for immune landscape, radiation resistance signatures, microenvironmental and tumor genome profiles and correlate radiation induced changes to tumor and patient characteristics and residual cancer burden.
XIII. To characterize irradiated normal breast and nodal tissues for genomic, proteomic, and metabolomic profiles and correlate these to tumor and patient characteristics, tumor burden, and toxicity.
XIV. To characterize irradiated normal breast and nodal tissues for genomic, proteomic, and metabolomic profiles and correlate these to tumor and patient characteristics, tumor burden, and toxicity.
XV. To compare surgical, radiation, and health services outcomes for patients treated with PreMRT on this trial to a matched cohort of patients treated with standard post-mastectomy radiation with breast reconstruction on the SAPHIRE protocol (2016-0142).
XVI. To compare translational data for patients treated with PreMRT on this trial to a matched cohort of patients treated with standard post-mastectomy radiation with breast reconstruction on the SAPHIRE protocol (2016-0142).
XVII. To pilot preMRT in a cohort of metastatic inflammatory breast cancer patients who will be undergoing standard of care neoadjuvant chemotherapy and mastectomy purely for local control.
XVIII. To examine DNA obtained from peripheral blood samples, including cell free DNA, before and after radiation in order to identify markers of normal tissue toxicity secondary to cancer treatment.
XIX. To examine patient imaging data and candidate peripheral blood markers, including those obtained from metabolomic, proteomic and cytokine/chemokine analysis, to better understand the impact of cancer treatment on cardiovascular disease.
OUTLINE: Patients are randomized to 1 of 2 arms. Patients with metastatic inflammatory breast cancer are assigned to arm II.
ARM I (HF-Pre-MRT): Patients receive hypofractionated RT for 15 fractions over 3-4 weeks on study. About 2-5 weeks after RT, patients undergo mastectomy and breast reconstructive surgery. Patients also undergo collection of blood throughout the trial and may undergo biopsy at baseline.
ARM II (CF-Pre-MRT): Patients receive conventionally fractionated RT for 25 fractions over 5-6 weeks on study. About 2-5 weeks after RT, patients undergo mastectomy and breast reconstructive surgery. Patients also undergo collection of blood throughout the trial and may undergo biopsy at baseline.
Upon completion of study treatment, patients undergo follow-up at 6, 12, and 18 months, at year 5, and then every year until year 10.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorBenjamin David Smith
- Primary ID2022-0880
- Secondary IDsNCI-2023-01985
- ClinicalTrials.gov IDNCT05774678