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Trial Title:
Trial Of PreoperAtive Radiation (TOPAz): A Randomized Trial Comparing Hypofractionated Versus Conventionally Fractionated Preoperative Radiation Followed by Mastectomy With Immediate Autologous Breast Reconstruction With Integrated Nanomechanical Biomarker Evaluation
NCT ID:
NCT05774678
Condition:
Breast Cancer
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Group 1 (preoperative radiation hypofractionated)
Description:
radiation schedules/regimens before your scheduled breast surgery
Arm group label:
Group 1 (preoperative radiation hypofractionated)
Arm group label:
Group 2 (preoperative radiation conventionally fractionated)
Intervention type:
Other
Intervention name:
Group 2 (preoperative radiation conventionally fractionated)
Description:
radiation schedules/regimens before your scheduled breast surgery
Arm group label:
Group 1 (preoperative radiation hypofractionated)
Arm group label:
Group 2 (preoperative radiation conventionally fractionated)
Summary:
To compare the outcomes of and responses to 2 different radiation therapy schedules (the
standard radiation amount and number of doses versus less radiation and fewer doses) that
are being given before having breast cancer surgery (cancer removal and reconstruction).
Detailed description:
Primary Objectives:
- To compare BREAST-Q satisfaction with breasts 18 months after reconstructive surgery
for patients randomized to HF-PreMRT versus CF-PreMRT. We hypothesize that HF-PreMRT
will be superior to CF-PreMRT with regard to this endpoint.
- To compare oncologic outcomes following HF-PreMRT versus CF-PreMRT, including
residual cancer burden, local-regional control, disease-free survival, and overall
survival.
- 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.
- To compare radiation outcomes following HF-PreMRT versus CF-PreMRT, including acute
and late toxicities and fibrosis.
Secondary Objectives:
- 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.
- To compare patient-reported quality of life and toxicities following HF-PreMRT
versus CF-PreMRT.
- To compare patient-reported quality of life and toxicities following HF-PreMRT
versus CF-PreMRT.
- To evaluate associations between the radiation treatment plan parameters and
surgical, radiation, health services, and patient-reported outcomes.
- To evaluate nanomechanical properties of the breast cancer before and after
radiation and their association with oncologic outcomes
- To evaluate nanomechanical properties of the breast normal tissue after radiation
and their association with surgical and radiation outcomes.
- To evaluate the association of germline polymorphisms, including the pro-fibrotic
cytokine transforming growth factor-beta (TGF-β), with circulating serum TGF-levels
during and after radiation and toxicities of radiation and reconstruction,
particularly fibrotic complications.
- 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.
- 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.
- 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
- 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.
- 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).
- 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).
- 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. These patients will not be evaluated in the primary trial
endpoints or Artidis studies.
- 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.
- 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.
Criteria for eligibility:
Criteria:
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 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 HER2 positive, non-IBC breast cancer treated with neoadjuvant
chemotherapy, one of the following criteria must be met:
1. 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.
2. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Benjamin D. Smith, MD
Phone:
713-563-2380
Email:
bsmith3@mdanderson.org
Investigator:
Last name:
Benjamin D. Smith, MD
Email:
Principal Investigator
Start date:
April 5, 2023
Completion date:
November 1, 2028
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Artidis
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05774678
http://www.mdanderson.org
