Adding Preoperative Radiotherapy Based on Early Treatment Response in Breast Cancer

NCT07892508 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RAPID-NeoBC-PT-2026
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

RAPID-NeoBC is a prospective, multicentre, response-adapted study with a randomized component for adults with operable, nonmetastatic invasive breast cancer receiving guideline-recommended neoadjuvant systemic therapy. After two treatment cycles, participants with stable disease on blinded central imaging review are randomized 1:1 to continue standard care alone or to receive standard care plus response-adapted preoperative radiotherapy. The primary outcome is centrally reviewed pathological complete response in the breast and sampled regional lymph nodes, defined as ypT0/is ypN0. Participants with complete or partial response continue standard care. Participants with disease progression may enter a nonrandomized radiotherapy rescue pathway if protocol criteria are met. Eligible participants are followed after surgery for recurrence, survival, safety, quality of life, function, and other protocol-defined outcomes.

Conditions

Invasive Breast Cancer

Keywords

Neoadjuvant therapy; Preoperative radiotherapy; Stereotactic body radiotherapy; Spatially fractionated radiotherapy; Lattice radiotherapy; Pathological complete response; Response-adapted treatment; Breast-conserving surgery; Axillary surgery de-escalation; Breast-specific gamma imaging; Magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response in the Breast and Regional Lymph Nodes

  Proportion of randomized participants with no residual invasive cancer in the breast, with ductal carcinoma in situ permitted, and no residual cancer in sampled regional lymph nodes, defined as ypT0/is ypN0 and determined by blinded central pathology review. Participants without evaluable surgery or pathology, or with death, progression preventing surgery, or an efficacy-driven nonprotocol preoperative treatment change, are classified as not achieving pathological complete response under the prespecified analysis rule.

  At definitive surgery after completion of planned neoadjuvant therapy; surgery is scheduled 3 to 6 weeks after the final planned systemic-therapy cycle and not earlier than 4 weeks after the last preoperative radiotherapy fraction.

Secondary Outcomes (15)

• Residual Cancer Burden

  At definitive surgery after neoadjuvant therapy.

• R0 Resection Rate

  At definitive surgery.

• Breast-Conserving Surgery Rate

  At definitive surgery.

• Axillary Surgery De-escalation Rate

  At preoperative strategy confirmation and definitive surgery.

• Three-Year Cumulative Incidence of First Locoregional Recurrence

  From date of first definitive surgery until the date of first documented ipsilateral invasive or in situ breast recurrence, ipsilateral chest-wall recurrence, or regional nodal recurrence, assessed up to 3 years after surgery.

Other Outcomes (10)

• Physician-Rated Cosmetic Outcome After Breast-Conserving Surgery（rated by the physician）

  12 months after surgery, then yearly through 5 years after surgery.

• Participant-Rated Cosmetic Outcome After Breast-Conserving Surgery (rated by the participant)

  12 months after surgery, then yearly through 5 years after surgery.

• Range of Motion on the Treated Side（goniometer, degrees）

  Baseline and 3, 6, and 12 months after surgery, then yearly through 5 years after surgery

Study Arms (4)

Responder Observation Pathway

OTHER

Participants with complete or partial response after two cycles continue physician-selected standard neoadjuvant systemic therapy without research preoperative radiotherapy.

Other: Guideline-recommended neoadjuvant systemic therapy; Diagnostic Test: Serial contrast-enhanced breast MRI and breast-specific gamma imaging

Randomized Control Standard Care

ACTIVE COMPARATOR

Participants with stable disease are randomized to continue physician-selected standard neoadjuvant systemic therapy without research preoperative radiotherapy.

Other: Guideline-recommended neoadjuvant systemic therapy; Diagnostic Test: Serial contrast-enhanced breast MRI and breast-specific gamma imaging

Randomized Experimental Standard Care plus neo-RT

EXPERIMENTAL

Participants with stable disease are randomized to standard neoadjuvant systemic therapy plus centrally reviewed response-adapted preoperative radiotherapy.

Radiation: Response-adapted preoperative radiotherapy; Other: Guideline-recommended neoadjuvant systemic therapy; Diagnostic Test: Serial contrast-enhanced breast MRI and breast-specific gamma imaging

Nonrandomized PD Rescue Cohort

EXPERIMENTAL

Participants with disease progression after two cycles undergo restaging and multidisciplinary review and may receive research preoperative radiotherapy unless a protocol-defined exemption applies.

Radiation: Response-adapted preoperative radiotherapy; Other: Guideline-recommended neoadjuvant systemic therapy; Diagnostic Test: Serial contrast-enhanced breast MRI and breast-specific gamma imaging

Interventions

Response-adapted preoperative radiotherapy RADIATION

Eligible breast primary tumors smaller than 5 cm receive 24 Gy in 3 fractions when stereotactic constraints are met. Tumors at least 5 cm, or tumors unsuitable for whole-target stereotactic treatment but eligible for spatially fractionated treatment, may receive a peripheral dose of 20 Gy in 5 fractions with intratumoral vertices of 66.7 Gy in 5 fractions. Pathologically confirmed regional nodes are treated according to size, anatomy, dose constraints, and central approval. All plans require prospective central quality-assurance review.

Also known as: neo-RT, SBRT, SFRT, lattice radiotherapy

Nonrandomized PD Rescue Cohort; Randomized Experimental Standard Care plus neo-RT

Guideline-recommended neoadjuvant systemic therapy OTHER

The treating physician and multidisciplinary team select a curative-intent regimen. The protocol does not assign, provide, or modify systemic therapy. HER2-positive disease includes anti-HER2 therapy, and at least six cycles or the regimen-defined complete course is planned.

Nonrandomized PD Rescue Cohort; Randomized Control Standard Care; Randomized Experimental Standard Care plus neo-RT; Responder Observation Pathway

Serial contrast-enhanced breast MRI and breast-specific gamma imaging DIAGNOSTIC_TEST

Paired examinations are performed at baseline, after cycle 2 and before cycle 3, and before surgery. MRI response is assessed centrally using RECIST 1.1 and directs response-adapted routing after cycle 2.

Nonrandomized PD Rescue Cohort; Randomized Control Standard Care; Randomized Experimental Standard Care plus neo-RT; Responder Observation Pathway

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years at the time of written informed consent.
• \. Histologically confirmed unilateral invasive breast cancer with documented estrogen receptor, progesterone receptor, HER2, and Ki-67 status.
• \. No prior systemic therapy, radiotherapy, or definitive surgery for the current breast cancer.
• \. Nonmetastatic disease on a curative-intent pathway; clinical stage cT1c to cT4c and cN0 to cN3, excluding cT4d inflammatory breast cancer.
• \. At least one measurable breast primary tumor with a longest diameter of 15 mm or greater on baseline contrast-enhanced MRI; paired baseline BSGI and required lesion marking completed. Multifocal or multicentric disease must meet protocol imaging requirements.
• \. Suspicious or confirmed involved regional lymph nodes have undergone protocol-required pathological confirmation and marking when applicable.
• \. ECOG performance status 0 or 1 and organ function adequate for planned systemic therapy, radiotherapy, and surgery.
• \. Able and willing to comply with MRI, BSGI, treatment, follow-up, and contraception requirements. Participants of childbearing potential must have a negative pregnancy test before examinations involving a radiopharmaceutical.
• \. A guideline-recommended, curative-intent neoadjuvant systemic therapy plan has been documented before entry. HER2-positive disease includes anti-HER2 therapy, and at least six cycles or the regimen-defined complete course is planned.

You may not qualify if:

• \. Distant metastatic disease, inflammatory breast cancer, or bilateral breast cancer requiring simultaneous definitive treatment.
• \. Prior radiotherapy to the ipsilateral breast, chest wall, or regional lymph nodes when cumulative dose constraints cannot be met.
• \. Pregnancy or breastfeeding, or inability to implement required contraception.
• \. Inability, in the investigator's judgment, to complete definitive surgery or key follow-up procedures.

Sponsors & Collaborators

• Second Affiliated Hospital, Zhejiang University, School of Medicine: lead

Study Sites (2)

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

Location

The Fourth Affiliated Hospital, Zhejiang University School of Medicine

Yiwu, Zhejiang, 322000, China

Location

Central Study Contacts

Jian Huang, PhD

CONTACT

0571-18768119248; drhuangjian@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study is open label for participants and treating investigators. The primary pathological endpoint is assessed by central pathologists who are not informed of randomized assignment. Imaging response routing and locoregional recurrence are also centrally reviewed under the protocol-defined procedures.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are routed after two treatment cycles according to blinded central MRI and BSGI review. Participants with stable disease are randomized 1:1 to standard care or standard care plus preoperative radiotherapy. Complete or partial responders continue standard care in a nonrandomized observation pathway. Participants with progressive disease may enter a nonrandomized radiotherapy rescue pathway. Eligible participants subsequently enter prospective surgical follow-up without protocol-assigned surgery.

Study Record Dates

• First Submitted: October 11, 2026
• First Posted: October 23, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): December 31, 2035
• Last Updated: October 23, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)