Invasive Breast CancerPhase 2RAPID-NeoBCNCT07892508
Adding Preoperative Radiotherapy Based on Early Treatment Response in Breast Cancer
A Phase 2 study testing Response-adapted preoperative radiotherapy, Guideline-recommended neoadjuvant systemic therapy and Serial contrast-enhanced breast MRI and breast-specific gamma imaging in people with Invasive Breast Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Invasive Breast Cancer
- What is being tested?
- Response-adapted preoperative radiotherapy, Guideline-recommended neoadjuvant systemic therapy and Serial contrast-enhanced breast MRI and breast-specific gamma imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 2 sitesChina
- Study dates
- 1 Nov 2026to 31 Dec 2035
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.Age 18 to 75 years at the time of written informed consent.
- 2. Histologically confirmed unilateral invasive breast cancer with documented estrogen receptor, progesterone receptor, HER2, and Ki-67 status.
- 3. No prior systemic therapy, radiotherapy, or definitive surgery for the current breast cancer.
- 4. Nonmetastatic disease on a curative-intent pathway; clinical stage cT1c to cT4c and cN0 to cN3, excluding cT4d inflammatory breast cancer.
- 5. 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.
- 6. Suspicious or confirmed involved regional lymph nodes have undergone protocol-required pathological confirmation and marking when applicable.
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- 7. ECOG performance status 0 or 1 and organ function adequate for planned systemic therapy, radiotherapy, and surgery.
- 8. 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.
- 9. 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.
Who cannot join
- 1. Distant metastatic disease, inflammatory breast cancer, or bilateral breast cancer requiring simultaneous definitive treatment.
- 2. Prior radiotherapy to the ipsilateral breast, chest wall, or regional lymph nodes when cumulative dose constraints cannot be met.
- 3. Active infection, interstitial lung disease, or another condition making planned standard therapy, research radiotherapy, or surgery unacceptably risky. Active autoimmune disease or organ transplantation is exclusionary only when contraindicated by the planned systemic-therapy component or considered an unacceptable risk by the multidisciplinary team.
- 4. Pregnancy or breastfeeding, or inability to implement required contraception.
- 5. Inability, in the investigator's judgment, to complete definitive surgery or key follow-up procedures.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009
The Fourth Affiliated Hospital, Zhejiang University School of Medicine
Yiwu, Zhejiang, 322000
De zhi Li, M.D., 0571-13757137421, 11418327@zju.edu.cn
About this study
Official title: RAPID-NeoBC Trial: Response-Adapted Preoperative Irradiation and De-escalated Surgery for Neoadjuvant Therapy in Breast Cancer - a Multicentre Prospective and Randomized Controlled Trial
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.
Read the detailed description
All participants receive guideline-recommended neoadjuvant systemic therapy selected by the treating physician and multidisciplinary team. The protocol does not assign the systemic regimen. Contrast-enhanced breast magnetic resonance imaging and breast-specific gamma imaging are performed at baseline and after two treatment cycles. Response routing is based on blinded independent central review.
Participants with stable disease are eligible for central 1:1 randomization to standard care alone or standard care plus response-adapted preoperative radiotherapy. Approximately 200 participants will be registered so that 44 participants with stable disease can be randomized (22 per arm; randomization capped at 50). Randomization is stratified by molecular subtype. Central pathologists who assess the primary endpoint are not informed of randomized assignment. Every research radiotherapy plan requires prospective central quality-assurance review and compliance with organ-at-risk constraints.
Participants with complete or partial response continue standard care without research radiotherapy. Participants with disease progression undergo restaging and multidisciplinary review and may enter a nonrandomized rescue pathway in which research radiotherapy is planned unless distant progression, dose constraints, medical risk, or participant preference precludes treatment. After neoadjuvant therapy, eligible participants enter prospective surgical follow-up. Surgery is selected through routine multidisciplinary care and is not assigned by the protocol.
- Conditions
- Invasive Breast Cancer
- Being tested
- Response-adapted preoperative radiotherapy, Guideline-recommended neoadjuvant systemic therapy, Serial contrast-enhanced breast MRI and breast-specific gamma imaging
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Response-adapted preoperative radiotherapyRadiation
Also called neo-RT, SBRT, SFRT, lattice radiotherapy
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.
Guideline-recommended neoadjuvant systemic therapyOther
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.
Serial contrast-enhanced breast MRI and breast-specific gamma imagingDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| Responder Observation Pathway | Other | Participants with complete or partial response after two cycles continue physician-selected standard neoadjuvant systemic therapy without research preoperative radiotherapy. Receives: 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. Receives: 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. Receives: 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. Receives: Radiation: Response-adapted preoperative radiotherapy; Other: Guideline-recommended neoadjuvant systemic therapy; Diagnostic Test: Serial contrast-enhanced breast MRI and breast-specific gamma imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Residual Cancer Burden continuous score and categories RCB-0, RCB-I, RCB-II, and RCB-III based on surgical pathology and central review.
Measured: At definitive surgery after neoadjuvant therapy.
R0 Resection Rate
Proportion of participants undergoing definitive surgery with microscopically margin-negative resection.
Measured: At definitive surgery.
Breast-Conserving Surgery Rate
Proportion of participants whose definitive breast procedure is breast-conserving surgery or a protocol-defined breast de-escalation procedure.
Measured: At definitive surgery.
Axillary Surgery De-escalation Rate
Proportion of participants entering the surgical cohort whose prespecified operative strategy avoids axillary lymph-node dissection and uses protocol-defined regional radiotherapy when indicated.
Measured: At preoperative strategy confirmation and definitive surgery.
Three-Year Cumulative Incidence of First Locoregional Recurrence
First ipsilateral invasive or in situ breast recurrence, ipsilateral chest-wall recurrence, or regional nodal recurrence after definitive surgery. Death and prior distant recurrence are treated as competing events.
Measured: 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.
Adverse Events and Serious Adverse Events
Incidence and maximum severity of adverse events and serious adverse events graded using Common Terminology Criteria for Adverse Events Version 6.0, with relationship to the research intervention recorded.
Measured: From study entry through 90 days after definitive surgery (up to approximately 9 months after study entry); protocol-defined late effects continue to be collected through 5 years after surgery.
Dose-Limiting Toxicity Related to Preoperative Radiotherapy
Preoperative-radiotherapy-related grade 3 or higher nonhematologic toxicity, including protocol-defined skin, pulmonary, cardiac, brachial-plexus, esophageal, surgical-delay, and wound-healing events.
Measured: From the first preoperative radiotherapy fraction through 90 days after surgery; for participants without definitive surgery, through 6 months after the first fraction.
Late Toxicity
Protocol-recorded pulmonary, cardiac, neurologic, breast-fibrosis, upper-limb, and other late toxicities graded using Common Terminology Criteria for Adverse Events Version 6.0.
Measured: From 90 days after surgery through 5 years after surgery.
Curative Surgery Conversion in the Progressive-Disease Rescue Cohort
Proportion of participants in the nonrandomized progressive-disease rescue cohort who undergo R0 definitive surgery. The primary descriptive denominator is participants who receive preoperative radiotherapy, with a sensitivity estimate among all participants assigned to the rescue cohort.
Measured: Within 6 months after central confirmation of progressive disease.
Event-free Survival
Time from randomization (randomized participants) or from study registration (nonrandomized pathways) to the first of: disease progression precluding definitive surgery; local, regional, or distant recurrence after surgery; contralateral invasive breast cancer; second primary invasive cancer; or death from any cause. Participants without an event are censored at the date of last disease assessment. Results are reported by randomized arm and descriptively for nonrandomized pathways.
Measured: From date of randomization (randomized participants) or date of study registration (nonrandomized pathways) until the date of first documented event as defined above or death from any cause, whichever came first, assessed up to 5 years after definitive s
Disease-free Survival
Among participants who undergo definitive surgery, time from surgery to the first of: invasive local, regional, or distant recurrence; contralateral invasive breast cancer; second primary invasive cancer; or death from any cause. Participants without an event are censored at the date of last disease assessment.
Measured: From date of definitive surgery until the date of first documented invasive local, regional, or distant recurrence, contralateral invasive breast cancer, second primary invasive cancer, or death from any cause, whichever came first, assessed up to 5 year
Overall Survival
Time from study registration (all participants) and from randomization (randomized participants) to death from any cause. Participants alive at last contact are censored at the date last known alive.
Measured: From date of study registration (all participants) or date of randomization (randomized participants) until date of death from any cause, assessed up to 5 years after definitive surgery (up to approximately 5.5 years after study entry).
Objective Imaging Response on Contrast-Enhanced Breast MRI
Proportion of participants with complete or partial response of breast and regional nodal disease on contrast-enhanced MRI according to RECIST 1.1, assessed by blinded independent central review. Concurrent breast-specific gamma imaging functional response is reported descriptively.
Measured: After completion of Cycle 2 and before the start of Cycle 3 (each cycle is 21 days), and before definitive surgery, which is planned approximately 18 to 24 weeks after study entry.
Reoperation Rate
Proportion of participants undergoing definitive surgery who require a further breast or axillary operation because of positive margins, wound non-healing, flap necrosis, or other surgical complications.
Measured: From definitive surgery through 90 days after surgery.
Change in EORTC QLQ-C30 Global Health Status/Quality of Life Score
Health-related quality of life measured with the EORTC QLQ-C30 and the breast cancer module QLQ-BR23, scored according to the EORTC QLQ-C30 Scoring Manual (3rd edition) on 0-100 scales. The key summary measure is the change in QLQ-C30 global health status/quality of life score from baseline to 12 months after surgery; functional and symptom scales are reported descriptively.
Measured: Baseline, after completion of Cycle 2 (each cycle is 21 days), before definitive surgery, and 3, 6, and 12 months after surgery, then yearly through 5 years after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Mar 2030 (estimated)
- Study completion31 Dec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07892508
- Sponsor's protocol ID
- RAPID-NeoBC-PT-2026
- Acronym
- RAPID-NeoBC
- Status last verified
- Sep 2026
- First submitted
- 11 Oct 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared outside the study team. Data from participants recruited in China are subject to the Regulations on the Management of Human Genetic Resources and the Personal Information Protection Law of the People's Republic of China, and the ethics approval does not cover external transfer of participant-level data. The study protocol and statistical analysis plan will be made available on ClinicalTrials.gov, and aggregate results will be posted and published.