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

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ClinicalTrials.gov Identifier: NCT05774678

Recruitment Status : Recruiting

First Posted : March 20, 2023

Last Update Posted : March 21, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

Artidis

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Tracking Information

First Submitted Date ^ICMJE

February 28, 2023

First Posted Date ^ICMJE

March 20, 2023

Last Update Posted Date

March 21, 2024

Actual Study Start Date ^ICMJE

April 5, 2023

Estimated Primary Completion Date

November 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 [ Time Frame: through study completion; an average of 1 year. ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Not Provided

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

Brief 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.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Breast Cancer

Intervention ^ICMJE

Radiation: Group 1 (preoperative radiation hypofractionated)
radiation schedules/regimens before your scheduled breast surgery
Other: Group 2 (preoperative radiation conventionally fractionated)
radiation schedules/regimens before your scheduled breast surgery

Study Arms ^ICMJE

Experimental: Group 1 (preoperative radiation hypofractionated)
Participants will receive the standard number of radiation treatment doses
Interventions:
- Radiation: Group 1 (preoperative radiation hypofractionated)
- Other: Group 2 (preoperative radiation conventionally fractionated)
Experimental: Group 2 (preoperative radiation conventionally fractionated)
Participants will receive the standard number of radiation treatment doses
Interventions:
- Radiation: Group 1 (preoperative radiation hypofractionated)
- Other: Group 2 (preoperative radiation conventionally fractionated)

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

126

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

November 1, 2028

Estimated Primary Completion Date

November 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Benjamin D. Smith, MD

(713) 563-2380

bsmith3@mdanderson.org

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT05774678

Other Study ID Numbers ^ICMJE

2022-0880
NCI-2023-01985 ( Other Identifier: NCI-CTRP Clinical Trials Registry )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

M.D. Anderson Cancer Center

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

M.D. Anderson Cancer Center

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Artidis

Investigators ^ICMJE

Principal Investigator:

Benjamin D. Smith, MD

M.D. Anderson Cancer Center

PRS Account

M.D. Anderson Cancer Center

Verification Date

March 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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