HER2-Negative Breast CancerPhase 2NCT07396454
Study on the Treatment of HER2-negative Breast Cancer Brain Metastases With Radiotherapy Combined With Anlotinib
A Phase 2 study testing Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor in people with HER2-Negative Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
Angiogenesis inhibition represents a significant therapeutic target in breast cancer; however, despite its theoretical feasibility, progress in advanced breast cancer has been slow. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- HER2-Negative Breast Cancer
- What is being tested?
- Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteChina
- Study dates
- 10 Feb 2026to 1 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients aged 18 to 70 years (calculated on the date of informed consent signing).
- Karnofsky Performance Status (KPS) score ≥ 70, or KPS = 60 primarily attributable to neurological symptoms.
- HER2-negative status confirmed by pathology from Jiangsu Provincial Hospital's Pathology Department. HER2 immunohistochemistry (IHC) must be (-) or (1+). Patients with HER2 IHC (2+) must have a negative result on confirmatory fluorescence in situ hybridization (FISH) testing.
- Presence of brain metastases confirmed by contrast-enhanced cranial MRI prior to enrollment. At least one measurable intracranial lesion is required according to RANO-BM criteria.
- If prior anti-tumor therapy (excluding treatments specifically targeting intracranial metastases) has been administered, a washout period of at least 2 weeks is required. Any prior treatment-related toxicities must have resolved to ≤ Grade 2 (CTCAE v3.0; excluding alopecia and hematological toxicities). Concurrent use of bisphosphonates, mannitol, corticosteroids, etc., is permitted during the study. Corticosteroid dosage must have been stable for at least one week prior to enrollment (e.g., dexamethasone ≤ 16 mg/day or equivalent).
- Life expectancy of at least 3 months.
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- Adequate organ and hematological function, meeting the following criteria:
- Hematology (without transfusion or growth factor support within 14 days):
- Hemoglobin (Hb) ≥ 80 g/L.
- Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L.
- Platelet count (PLT) ≥ 50 × 10⁹/L.
- Biochemistry:
- Total bilirubin (TBIL) < 1.5 × upper limit of normal (ULN), or ≤ 3 × ULN in patients with liver metastases.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, or ≤ 5 × ULN in patients with liver metastases.
- Serum creatinine (Cr) ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula).
- Magnesium ≥ lower limit of normal (LLN).
- Women of childbearing potential must be surgically sterile, postmenopausal, or agree to use highly effective contraception (e.g., oral contraceptives, intrauterine device, sexual abstinence, or barrier methods with spermicide) during the study and for 6 months after the final dose. A negative serum pregnancy test within 7 days prior to enrollment is required for all non-sterile, premenopausal women (positive results must be ruled out as false-positive by ultrasound). Patients must not be breastfeeding.
- Voluntary participation with written informed consent.
Who cannot join
- Patients with extensive leptomeningeal metastasis or hemorrhagic brain metastases.
- Patients with uncontrolled seizures.
- Patients with any other severe and/or poorly controlled concurrent medical condition that, in the investigator's judgment, prohibits their participation in this clinical study, including but not limited to:
- Factors significantly affecting oral drug intake (e.g., inability to swallow, chronic diarrhea, intestinal obstruction).
- Known hypersensitivity to anlotinib or any component of the investigational product.
- History of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
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- Clinically significant cardiovascular disease (defined as: unstable angina, symptomatic congestive heart failure of New York Heart Association [NYHA] Class ≥ II, uncontrolled severe arrhythmia), or myocardial infarction within 6 months prior to enrollment.
- Active or uncontrolled infection requiring systemic treatment within 2 weeks prior to enrollment (excluding simple urinary tract infections or upper respiratory tract infections).
- History of concurrent other malignancies, except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- Patients who are pregnant, breastfeeding, or planning to become pregnant during the treatment period or within 6 months after treatment completion.
- Patients (including female patients and/or their male partners) unwilling to use effective contraception during the treatment period and for 6 months after treatment completion.
- Patients ineligible for contrast-enhanced MRI examinations.
- Patients who have previously received anti-angiogenic TKI therapy and experienced intracranial progression (Note: Patients who received prior anti-angiogenic TKI therapy without subsequent disease progression are eligible. Patients previously treated with anti-angiogenic macromolecular agents, such as bevacizumab, are eligible).
- Patients with a history of other malignancies within the past 5 years or concurrent other malignancies, except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix. (Note: This appears to be a duplicate of criterion 3f. In standard protocols, it is typically listed once.).
- Patients unwilling or unable to comply with scheduled follow-up as required by the study protocol.
- Any other condition assessed by the investigator that may affect the patient's compliance with the protocol or the evaluation of study endpoints, rendering the patient unsuitable for study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Nanjing Medical University
Nanjing
MingHui Zhao, 025-68306360
About this study
Official title: A Prospective, Single-Arm, Phase II Clinical Study of Radiotherapy Combined With Anlotinib and a Tubulin Inhibitor for the Treatment of HER2-Negative Breast Cancer With Brain Metastases
Angiogenesis inhibition represents a significant therapeutic target in breast cancer; however, despite its theoretical feasibility, progress in advanced breast cancer has been slow. Currently, there is a lack of prospective data supporting the selection of tyrosine kinase inhibitors (TKIs) in combination with local therapy. This phase II study aims to evaluate the efficacy and safety of stereotactic radiotherapy (SRT) or whole-brain radiotherapy (WBRT) combined with anlotinib in patients with HER2-negative advanced breast cancer and brain metastases.
Read the detailed description
Angiogenesis inhibition represents a significant therapeutic target in breast cancer; however, despite its theoretical feasibility, progress in advanced breast cancer has been slow. Currently, there is a lack of prospective data supporting the selection of tyrosine kinase inhibitors (TKIs) in combination with local therapy. This phase II study aims to evaluate the efficacy and safety of stereotactic radiotherapy or whole-brain radiotherapy (WBRT) combined with anlotinib in patients with HER2-negative advanced breast cancer and brain metastases.
- Conditions
- HER2-Negative Breast Cancer
- Being tested
- Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiotherapy Combined with Anlotinib and a Microtubule InhibitorDrug
Based on the size, location and number of brain metastases, an appropriate radiotherapy plan is given. Arloxitin can be used starting from the 1st day after radiotherapy to within 1 week.
Arloxitin 12 mg, qd (it is recommended to take it before meals and take the medicine at the same time every day), take orally continuously for 2 weeks and then stop for 1 week. A 21-day period constitutes one treatment cycle. During the medication period, if there is a missed dose, if the time from the missed dose to the next dose is less than 12 hours, no additional dose will be given.
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor | Experimental | Based on the size, location and number of brain metastases, an appropriate radiotherapy plan is given. Arloxitin can be used starting from the 1st day after radiotherapy to within 1 week.
Arloxitin 12 mg, qd (it is recommended to take it before meals and take the medicine at the same time every day), take orally continuously for 2 weeks and then stop for 1 week. A 21-day period constitutes one treatment cycle. During the medication period, if there is a missed dose, if the time from the missed dose to the next dose is less than 12 hours, no additional dose will be given. Receives: Drug: Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central nervous system progression-free survival (CNS-PFS) rate
According to the RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) standard, the 12-month central nervous system progression-free survival (CNS-PFS) rate was determined by at least two experienced neuro-radiologists.
Measured: 12months
Secondary outcomes (7)
Central nervous system progression-free survival (CNS-PFS)
It is defined as the time from the start of the study treatment for the subject until the first imaging confirmation of intracranial disease progression (PD) or any cause of death. The assessment of intracranial lesions is based on the RANO-BM standard.
Measured: 12months
Progression free survival（PFS）
It is defined as the time from the start of the study treatment for the subject until the first imaging confirmation of disease progression (PD) or death due to any cause. The assessment of intracranial lesions is based on the RANO-BM criteria, while the assessment of extracranial lesions is based on the RECIST 1.1 criteria.
Measured: 12months
Overall survival（OS）
It is defined as the period from the date of receiving the study treatment to the date of death (due to any cause). For subjects who did not experience death, the analysis will be truncated at the time of confirmed survival.
Measured: 12months
Objective Response Rate of the Central Nervous System (CNS-ORR)
It is defined as the percentage of subjects who achieved complete or partial responses in the central nervous system from the time they began receiving treatment in this study until they left the study group. The assessment is conducted using the RANO-BM criteria.
Measured: 12months
Karnofsky Performance Status (KPS) score
The assessment was conducted using the Karnofsky Performance Status.
Measured: 12months
Adverse event（AE）
AEs are recorded according to the NCI CTCAE 5.0 standard
Measured: 12months
Simple Mental State Examination (MMSE) score
The assessment was conducted using the Mini-Mental State Examination (MMSE).
Measured: 12months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2026
- Study start10 Feb 2026 (estimated)
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07396454
- Sponsor's protocol ID
- 2025-SR-691
- Status last verified
- Feb 2026
- First submitted
- 1 Feb 2026
- Last updated
- 9 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Single-Arm, Phase II Clinical Study of Radiotherapy Combined With Anlotinib and a Tubulin Inhibitor for the Treatment of HER2-Negative Breast Cancer With Brain Metastases
- ClinicalTrials.gov ID
- NCT07396454
- Acronym / sponsor ID
- 2025-SR-691
- Conditions
- HER2-Negative Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 10 Feb 2026 (estimated)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 9 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Angiogenesis inhibition represents a significant therapeutic target in breast cancer; however, despite its theoretical feasibility, progress in advanced breast cancer has been slow. Currently, there is a lack of prospective data supporting the selection of tyrosine kinase inhibitors (TKIs) in combination with local therapy. This phase II study aims to evaluate the efficacy and safety of stereotactic radiotherapy (SRT) or whole-brain radiotherapy (WBRT) combined with anlotinib in patients with HER2-negative advanced breast cancer and brain metastases.
Detailed description
Angiogenesis inhibition represents a significant therapeutic target in breast cancer; however, despite its theoretical feasibility, progress in advanced breast cancer has been slow. Currently, there is a lack of prospective data supporting the selection of tyrosine kinase inhibitors (TKIs) in combination with local therapy. This phase II study aims to evaluate the efficacy and safety of stereotactic radiotherapy or whole-brain radiotherapy (WBRT) combined with anlotinib in patients with HER2-negative advanced breast cancer and brain metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor | Experimental | Drug: Radiotherapy Combined with Anlotinib and a Microtubule InhibitorBased on the size, location and number of brain metastases, an appropriate radiotherapy plan is given. Arloxitin can be used starting from the 1st day after radiotherapy to within 1 week. Arloxitin 12 mg, qd (it is recommended to take it before meals and take the medicine at the same time every day), take orally continuously for 2 weeks and then stop for 1 week. A 21-day period constitutes one treatment cycle. During the medication period, if there is a missed dose, if the time from the missed dose to the next dose is less than 12 hours, no additional dose will be given. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Female patients aged 18 to 70 years (calculated on the date of informed consent signing).
- Karnofsky Performance Status (KPS) score ≥ 70, or KPS = 60 primarily attributable to neurological symptoms.
- HER2-negative status confirmed by pathology from Jiangsu Provincial Hospital's Pathology Department. HER2 immunohistochemistry (IHC) must be (-) or (1+). Patients with HER2 IHC (2+) must have a negative result on confirmatory fluorescence in situ hybridization (FISH) testing.
- Presence of brain metastases confirmed by contrast-enhanced cranial MRI prior to enrollment. At least one measurable intracranial lesion is required according to RANO-BM criteria.
- If prior anti-tumor therapy (excluding treatments specifically targeting intracranial metastases) has been administered, a washout period of at least 2 weeks is required. Any prior treatment-related toxicities must have resolved to ≤ Grade 2 (CTCAE v3.0; excluding alopecia and hematological toxicities). Concurrent use of bisphosphonates, mannitol, corticosteroids, etc., is permitted during the study. Corticosteroid dosage must have been stable for at least one week prior to enrollment (e.g., dexamethasone ≤ 16 mg/day or equivalent).
Key exclusion criteria (16 listed)
- Patients with extensive leptomeningeal metastasis or hemorrhagic brain metastases.
- Patients with uncontrolled seizures.
- Patients with any other severe and/or poorly controlled concurrent medical condition that, in the investigator's judgment, prohibits their participation in this clinical study, including but not limited to:
- Patients who are pregnant, breastfeeding, or planning to become pregnant during the treatment period or within 6 months after treatment completion.
- Patients (including female patients and/or their male partners) unwilling to use effective contraception during the treatment period and for 6 months after treatment completion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiotherapy Combined with Anlotinib and a Microtubule InhibitorBased on the size, location and number of brain metastases, an appropriate radiotherapy plan is given. Arloxitin can be used starting from the 1st day after radiotherapy to within 1 week. Arloxitin 12 mg, qd (it is recommended to take it before meals and take the medicine at the same time every day), take orally continuously for 2 weeks and then stop for 1 week. A 21-day period constitutes one treatment cycle. During the medication period, if there is a missed dose, if the time from the missed dose to the next dose is less than 12 hours, no additional dose will be given. | Drug | Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor |
Primary outcome
Central nervous system progression-free survival (CNS-PFS) rate
Time frame: 12months
According to the RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) standard, the 12-month central nervous system progression-free survival (CNS-PFS) rate was determined by at least two experienced neuro-radiologists.
7 secondary outcomes
Central nervous system progression-free survival (CNS-PFS)
Time frame: 12months
Progression free survival（PFS）
Time frame: 12months
Overall survival（OS）
Time frame: 12months
Objective Response Rate of the Central Nervous System (CNS-ORR)
Time frame: 12months
Karnofsky Performance Status (KPS) score
Time frame: 12months
Adverse event（AE）
Time frame: 12months
Simple Mental State Examination (MMSE) score
Time frame: 12months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiotherapy Combined with Anlotinib and a Microtubule Inhibitor in people with HER2-Negative Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chi Zhang (025-83714511, jsphkj@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central nervous system progression-free survival (CNS-PFS) rate (time frame: 12months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.