Triple-negative Breast CancerNCT06371274
A Study on the Efficacy and Safety of Oral All-trans Retinoic Acid Combined With Toripalimab in TNBC.
A study testing ATRA and Toripalimab in people with Triple-negative Breast Cancer, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial summary
To evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple-negative Breast Cancer
- What is being tested?
- ATRA and Toripalimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteChina
- Study dates
- 10 Oct 2024to 30 Apr 2026
- Phase
- Interventional
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years at the time of signing the informed consent form;
- Pathologically confirmed as triple-negative breast cancer based on recent biopsy or other pathological specimens, with histological and/or cytological diagnosis;
- Patients with unresectable locally advanced or metastatic triple-negative breast cancer who have failed at least second-line standard treatment regimens;
- According to RECIST 1.1, at least one measurable lesion is required. Patients with only skin lesions or bone lesions are not eligible for inclusion;
- Adequate organ and bone marrow function (not received blood transfusions, recombinant human platelet growth factor, or colony-stimulating factor treatment in the 2 weeks before screening);
- The subject voluntarily agrees to participate in this study, signs the informed consent form, and is able to comply with the visits and related procedures specified in the protocol.
Who cannot join
- Known symptomatic or uncontrolled brain metastasis or other central nervous system (CNS) metastases;
- Patients with other malignant tumors, excluding those with cured basal cell or squamous cell skin carcinoma or in situ cervical cancer. Patients with other malignant tumors must have a disease-free interval of at least 5 years;
- Any severe and/or uncontrolled concurrent illness that hinders the patient's participation in the study;
- History of immunodeficiency, autoimmune diseases, the need for immunosuppressive therapy (daily dose \>10 mg of prednisone or equivalent), or a history of chronic infections;
- History of deep vein thrombosis or pulmonary embolism;
- Severe osteoporosis or patients with bone metastases;
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- Participants who, within the first 4 weeks before the initiation of the study treatment or during the 5 half-lives of any drugs used in the pre-study period (whichever is shorter), have received any chemotherapy, immunotherapy, biologic therapy, or participated in other drug clinical trials, or received traditional Chinese medicine preparations for the treatment of approved anticancer indications or radiotherapy within the first 2 weeks before the initiation of the study treatment, or have undergone major surgery within the first 4 weeks before the initiation of the study treatment;
- Patients with active hepatitis B or C; known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); positive syphilis antibody test;
- History of severe drug allergies or known allergy to any component of the investigational drug as per the prescription;
- The investigator considers the participant unsuitable for the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Meihua Lin, MS contact
China1 site, 1 recruiting
- Recruiting
The first affiliated hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang Province, P.R. China, 310003
Meihua Lin, MS
Jian Liu, MS
About this study
Official title: Efficacy and Safety Study of Oral All-trans Retinoic Acid Combined With Toripalimab in Patients With Inoperable Locally Advanced, Recurrent, or Metastatic Triple-negative Breast Cancer Who Had Failed Prior Second-line or Higher Standard Therapy.
To evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent therapy.
Read the detailed description
The study is designed as a single arm, open-label, mono-center exploratory trial, aiming to evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, unresectable, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent standard treatments. 32 subjects are planned to be enrolled. Eligible participants are subjected to take all-trans retinoic acid orally at a dose of 150 mg/m2 per day, twice a day for three consecutive days per cycle (d0~d2), and intravenous infusion of PD-1 monoclonal antibody at a dose of 240 mg on day 1 of each cycle (d1), with cycles repeated every 3 weeks until disease progression, death, loss to follow-up, intolerable toxicity, or meeting other withdrawal or termination criteria (whichever occurs first), for a maximum duration of 2 years. Each subject's study process includes a screening period (within 28 days), a treatment period, and a follow-up period. Subjects will sign the informed consent form and complete all baseline assessments during the screening period. Qualified subjects will enter the treatment period, followed by the survival follow-up every 3 months after the completion of the treatment period. Tumor assessments (contrast-enhanced CT) will be conducted every 2 cycles (6 weeks) during the combination treatment period, and efficacy evaluation will be based on RECIST 1.1 criteria. Moreover, iORR and iPFS were assessed by investigators based on iRECIST criteria. Adverse events will be assessed using NCI-CTCAE version 5.0, with observation of adverse events up to 30 days after the last treatment.
- Conditions
- Triple-negative Breast Cancer
- Being tested
- ATRA, Toripalimab
- Keywords
- all-trans retinoic acid, Toripalimab, triple-negative breast cancer, efficacy, safety
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATRADrug
ATRA is the main active metabolite of vitamin A. Studies have shown that ATRA can also reduce the number of MDSC in solid tumor patients, promote their differentiation and maturation, remove the immunosuppressive ability of MDSC, improve the tumor immune microenvironment, and thus improve the tumor treatment efficacy.
ToripalimabDrug
Toripalimab is a fully human monoclonal antibody injection against PD-1 receptor. The NMPA has accepted the application of Toripalimab for a new indication for the treatment of initial metastatic or relapsed metastatic TNBC with PD-L1 positive (CPS≥1).
| Study group | Role | What they receive |
|---|---|---|
| ATRA+Toripalimab | Experimental | Eligible participants are subjected to take all-trans retinoic acid orally at a dose of 150 mg/m2 per day, twice a day for three consecutive days per cycle (d0~d2), and intravenous infusion of PD-1 monoclonal antibody at a dose of 240 mg on day 1 of each cycle (d1), with cycles repeated every 3 weeks until disease progression, death, loss to follow-up, intolerable toxicity, or meeting other withdrawal or termination criteria (whichever occurs first), for a maximum duration of 2 years. Receives: Drug: ATRA; Drug: Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
During the combined therapy, tumor assessment (enhanced CT) is conducted every 2 cycles (6 weeks), and the efficacy is evaluated using the RECIST 1.1 criteria. ORR will be summarized as the proportion of subjects achieving objective tumor responses (complete response or partial response). ORR and its 95% confidence interval will be calculated.
Measured: up to 2 years
Secondary outcomes (3)
Progression-Free Survival (PFS)
PFS defined as the time from enrollment until disease progression or death (whichever occurs first).
Measured: up to 2 years
Duration of Response (DOR)
For responders (complete response or partial response), DOR is defined as the time from the earliest date meeting the response criteria to disease progression or death for any reason (whichever occurs first). For subjects who do not experience progression after meeting response criteria and continue to survive, DOR will be censored at the last evaluable tumor assessment date or the last follow-up date for disease progression.
Measured: up to 2 years
Overall Survival (OS)
OS is defined as the time interval between the date of the first dose and the date of death for any reason. Kaplan-Meier methodology will be used to estimate median OS, OS rates, and their 95% confidence intervals at different time points.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2024
- Study start10 Oct 2024
- Primary completion30 Apr 2026 (estimated)
- Study completion30 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple-negative Breast CancerStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Longfine Biotechnology Co., Ltd., TopAlliance
- Responsible party
- Principal investigator, Jian Liu, First Affiliated Hospital of Zhejiang University
- Investigators
- Xiaochen Zhang, MD, Principal investigator, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06371274
- Sponsor's protocol ID
- ZYYY-IIT-TNBC-001
- Status last verified
- Aug 2025
- First submitted
- 2 Apr 2024
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- 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 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety Study of Oral All-trans Retinoic Acid Combined With Toripalimab in Patients With Inoperable Locally Advanced, Recurrent, or Metastatic Triple-negative Breast Cancer Who Had Failed Prior Second-line or Higher Standard Therapy.
- ClinicalTrials.gov ID
- NCT06371274
- Acronym / sponsor ID
- ZYYY-IIT-TNBC-001
- Conditions
- Triple-negative Breast Cancer
- Keywords
- all-trans retinoic acid, Toripalimab, triple-negative breast cancer, efficacy, safety
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Collaborators
- Shanghai Longfine Biotechnology Co., Ltd., TopAlliance
- Study start
- 10 Oct 2024 (actual)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 30 Apr 2026 (estimated)
- First posted
- 17 Apr 2024 (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.
To evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent therapy.
Detailed description
The study is designed as a single arm, open-label, mono-center exploratory trial, aiming to evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, unresectable, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent standard treatments. 32 subjects are planned to be enrolled. Eligible participants are subjected to take all-trans retinoic acid orally at a dose of 150 mg/m2 per day, twice a day for three consecutive days per cycle (d0~d2), and intravenous infusion of PD-1 monoclonal antibody at a dose of 240 mg on day 1 of each cycle (d1), with cycles repeated every 3 weeks until disease progression, death, loss to follow-up, intolerable toxicity, or meeting other withdrawal or termination criteria (whichever occurs first), for a maximum duration of 2 years. Each subject's study process includes a screening period (within 28 days), a treatment period, and a follow-up period. Subjects will sign the informed consent form and complete all baseline assessments during the screening period. Qualified subjects will enter the treatment period, followed by the survival follow-up every 3 months after the completion of the treatment period. Tumor assessments (contrast-enhanced CT) will be conducted every 2 cycles (6 weeks) during the combination treatment period, and efficacy evaluation will be based on RECIST 1.1 criteria. Moreover, iORR and iPFS were assessed by investigators based on iRECIST criteria. Adverse events will be assessed using NCI-CTCAE version 5.0, with observation of adverse events up to 30 days after the last treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATRA+Toripalimab | Experimental | Drug: ATRA, Drug: ToripalimabEligible participants are subjected to take all-trans retinoic acid orally at a dose of 150 mg/m2 per day, twice a day for three consecutive days per cycle (d0~d2), and intravenous infusion of PD-1 monoclonal antibody at a dose of 240 mg on day 1 of each cycle (d1), with cycles repeated every 3 weeks until disease progression, death, loss to follow-up, intolerable toxicity, or meeting other withdrawal or termination criteria (whichever occurs first), for a maximum duration of 2 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years at the time of signing the informed consent form;
- Pathologically confirmed as triple-negative breast cancer based on recent biopsy or other pathological specimens, with histological and/or cytological diagnosis;
- Patients with unresectable locally advanced or metastatic triple-negative breast cancer who have failed at least second-line standard treatment regimens;
- According to RECIST 1.1, at least one measurable lesion is required. Patients with only skin lesions or bone lesions are not eligible for inclusion;
- Adequate organ and bone marrow function (not received blood transfusions, recombinant human platelet growth factor, or colony-stimulating factor treatment in the 2 weeks before screening);
Key exclusion criteria (10 listed)
- Known symptomatic or uncontrolled brain metastasis or other central nervous system (CNS) metastases;
- Patients with other malignant tumors, excluding those with cured basal cell or squamous cell skin carcinoma or in situ cervical cancer. Patients with other malignant tumors must have a disease-free interval of at least 5 years;
- Any severe and/or uncontrolled concurrent illness that hinders the patient's participation in the study;
- History of immunodeficiency, autoimmune diseases, the need for immunosuppressive therapy (daily dose \>10 mg of prednisone or equivalent), or a history of chronic infections;
- History of deep vein thrombosis or pulmonary embolism;
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 |
|---|---|---|
| ATRAATRA is the main active metabolite of vitamin A. Studies have shown that ATRA can also reduce the number of MDSC in solid tumor patients, promote their differentiation and maturation, remove the immunosuppressive ability of MDSC, improve the tumor immune microenvironment, and thus improve the tumor treatment efficacy. | Drug | ATRA+Toripalimab |
| ToripalimabToripalimab is a fully human monoclonal antibody injection against PD-1 receptor. The NMPA has accepted the application of Toripalimab for a new indication for the treatment of initial metastatic or relapsed metastatic TNBC with PD-L1 positive (CPS≥1). | Drug | ATRA+Toripalimab |
Primary outcome
Objective Response Rate (ORR)
Time frame: up to 2 years
During the combined therapy, tumor assessment (enhanced CT) is conducted every 2 cycles (6 weeks), and the efficacy is evaluated using the RECIST 1.1 criteria. ORR will be summarized as the proportion of subjects achieving objective tumor responses (complete response or partial response). ORR and its 95% confidence interval will be calculated.
3 secondary outcomes
Progression-Free Survival (PFS)
Time frame: up to 2 years
Duration of Response (DOR)
Time frame: up to 2 years
Overall Survival (OS)
Time frame: up to 2 years
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 12 Aug 2025.
- 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.
Meihua Lin, MS contact
Xiaochen Zhang, MD principal investigator
First Affiliated Hospital of Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ATRA and Toripalimab in people with Triple-negative Breast Cancer, run by First Affiliated Hospital of Zhejiang 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 6 inclusion and 10 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 12 Aug 2025. 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.
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 Jian Liu, MS (+86-0571-87236537, lindaliu87@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: up to 2 years). 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 12 Aug 2025.