Breast CancerPhase 2NCT06401005
SBRT, Chemotherapy, and AK104 Neoadjuvant Therapy for Triple-negative Breast Cancer (TNBC)
A Phase 2 study testing Cadonilimab (AK104) in people with Breast Cancer, run by Hubei Cancer Hospital at 1 site in China.
Trial summary
Studies have indicated that the improvement in pathological complete response (pCR) is significantly correlated with triple-negative breast cancer（TNBC）patients' overall survival (OS). Patients with TNBC have poor efficacy for neoadjuvant chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Cadonilimab (AK104)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteChina
- Study dates
- 28 Nov 2024to 1 Sep 2027
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed ER-/PR-/HER2- invasive breast cancer patients (ER/PR immunohistochemistry negative or<1%; Her2 immunohistochemistry of 0, 1+, or 2+/FISH-) patients; patients meeting one of the following conditions: (1) tumor mass larger than 2cm, (2) the presence of axillary lymph node metastasis, and (3) the desire to conserve breasts, but the ratio of tumor size to breast volume is large and difficult to conserve breasts;
- Patients aged ≥18 years old;
- ECOG score of 0-1;
- Biochemical test indexes before enrollment must meet the following criteria, hematologic: white blood cell count (WBC) ≥ 2.0x10^9/L; neutrophil count (ANC) ≥ 1.5×10^9/L; platelet count (PLT) ≥ 100×10^9/L; hemoglobin (Hb) ≥ 90g/L; function: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); glutamate aminotransferase (ALT) ≤3 × ULN; aspartate aminotransferase (AST) ≤3 × ULN; renal function: creatinine (Cr) ≤1.5 × ULN; if >1.5 × ULN, creatinine clearance needs to be ≥50mL/min (calculated according to Cockcroft-Gault formula); coagulation: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN.
Who cannot join
- Received chemotherapy, targeted therapy, or radiation therapy within 12 months prior to first use of study drug;
- Solid organ or blood system transplantation;
- Myocardial infarction, poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) within 6 months prior to first use of study drug (QTc intervals are calculated using the Fridericia formula, which is: QTc=QT/RR ^0.33);
- Class III-IV cardiac insufficiency according to NYHA criteria or cardiac ultrasound: LVEF < 50%;
- poorly controlled hypertension (defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg), previous hypertensive crisis or hypertensive encephalopathy;
- Human immunodeficiency virus (HIV) infection, HIV-positive; active tuberculosis; previous and current subjects with interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonitis, and severely impaired lung function that may interfere with the detection and management of suspected drug-associated pulmonary toxicity;
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- Known active or suspected autoimmune disease;
- Subjects who are allowed to enroll in a stable state and do not require systemic immunosuppressive therapy;
- Who have received a live vaccine within 28 days prior to the first use of study drug; however, inactivated viral vaccines for seasonal influenza are allowed;
- Who require systemic treatment with corticosteroids (> 10 mg/day prednisone equivalent dose) or other immunosuppressive medications within 14 days prior to the first use of study drug or for the duration of the study. Subjects. However, enrollment will be permitted in the absence of active autoimmune disease if the subject is treated with topical or inhaled steroids (low potency), systemic short-term use in small doses, single paracortical/intra-articular injections, or adrenocorticotropic hormone replacement therapy at a dose of ≤ 10 mg/day prednisone equivalent; and if any active infections that require systemic administration of Active infection requiring systemic administration of anti-infective therapy; subjects receiving prophylactic antibiotic therapy (e.g., for prevention of urinary tract infections or chronic obstructive pulmonary disease) are eligible for enrollment;
- Hepatitis B (those with a positive Hepatitis B Surface Antigen [HBsAg] or Hepatitis B Core Antibody [HBcAb] test and positive Hepatitis B Virus Deoxyribonucleic Acid [HBV-DNA] test), Hepatitis C (those with a positive Hepatitis C Virus [HCV] antibody test and positive Hepatitis C Virus [HBV] antibody test), and Hepatitis C (those with a positive Hepatitis B virus [HCV] antibody test and positive Hepatitis C Virus [HCV] antibody test) antibody test positive and hepatitis C virus ribonucleic acid [HCV-RNA] test positive); subjects with hepatitis B and hepatitis C co-infection (positive HBsAg or HBcAb test and positive HCV antibody test);
- Who have received other antibodies/drugs targeting immune checkpoints in the past, such as anti-PD-1, anti-PD-L1, anti-cytotoxic T-lymphocyte associated antigen- 4 (CTLA-4), and anti-cytotoxic T-lymphocyte associated antigen- 4 (CTLA-4). 4 (CTLA-4), etc.; are participating in another clinical study or are planning to start this study treatment less than 14 days from the end of treatment in the previous clinical study;
- Have undergone major surgery within 4 weeks prior to the first dose of study drug. Definition of major surgery for this study: surgery that requires at least 3 weeks of postoperative recovery time before receiving treatment on this study. Tumor puncture or lymph node excision biopsy allowed for enrollment;
- Pregnant or lactating females with a known history of severe allergy to any monoclonal antibody or the study drug and its excipients;
- Known history of psychotropic substance abuse or drug use; discontinued use of alcohol allowed for enrollment;
- Subjects with other factors that, in the judgment of the investigator, make them unsuitable for participation in this study.
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
Hubei Cancer Hospital
Wuhan, Hubei, 430079
Han Guang, MD
Han Guang, MD
About this study
Official title: A Single-arm, Open, Phase II Clinical Study of SBRT, Chemotherapy, and Cadonilimab (AK104) Neoadjuvant Therapy for Triple-negative Breast Cancer (TNBC)
Studies have indicated that the improvement in pathological complete response (pCR) is significantly correlated with triple-negative breast cancer（TNBC）patients' overall survival (OS). Patients with TNBC have poor efficacy for neoadjuvant chemotherapy. The combination of neoadjuvant therapy with immunotherapy and chemotherapy has been demonstrated to enhance the pCR rate of TNBC patients, increasing it from 45% to approximately 60%. Therefore, how to further improve the pCR rate of TNBC breast cancer became the main objective of this study. Stereotactic radiotherapy (SBRT) not only kills tumor cells directly, but also kills the distant unirradiated tumor cells by promoting the cross-initiation of tumor-specific CD8+ T cells, a phenomenon known as the abscopal effect. Our research team has recently discovered that the triple therapy model of SBRT + anti-vascular targeting + anti-PD-1 was safe and efficacious in lung cancer patients. Cadonilimab (AK104) is an PD-1/CTLA-4 bispecific antibody. In order to improve the pCR, a single-arm, open, phase II clinical study was proposed to explore the safety and efficacy of SBRT+AK104+chemotherapy, a neoadjuvant treatment modality, in the treatment of TNBC.
- Conditions
- Breast Cancer
- Being tested
- Cadonilimab (AK104)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cadonilimab (AK104)Drug
8Gy*3 SBRT to irradiate the primary lesion (without axillary lymph node metastasis) or 6Gy*3 SBRT irradiation to irradiate the primary lesion and axillary lymph node metastasis will be administered at first. And then the first cycle of chemotherapy+AK104 given within 24 hours of the end of SBRT. The total eight cycles of preoperative chemotherapy combined with immunotherapy were administered. Surgical resection was performed within 4-6 weeks after the completion of the eighth cycle of chemotherapy combined with immunotherapy. The chemotherapy regimen consisted of: Four cycles of doxorubicin 50mg/m2 (Q3W) + cyclophosphamide 600mg/m2 (Q3W) were administered, followed by four cycles of sequential albumin paclitaxel (125 mg/m2, d1, d8) and carboplatin (AUC=6, d1, Q3W) for 4 cycles. Postoperative completion of 9 cycles of immunotherapy was continued ± the need for postoperative adjuvant radiotherapy was confirmed based on the patient's preoperative status.
| Study group | Role | What they receive |
|---|---|---|
| TNBC patients | Experimental | Not described Receives: Drug: Cadonilimab (AK104) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete pathologic remission (pCR) rate
pCR is defined as ypT0/Tis and ypN0
Measured: Up to the 30 weeks
Secondary outcomes (3)
Objective response rate
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
Measured: Up to the 30 weeks
EFS
Event free survival
Measured: Up to 12 months after surgery
Quality of life assessment
Using the EORTC QLQ-BR2. It is based on the core cancer scale EORTCQLQ1-C30 with 23 additional scales specific to breast cancer patients. The questions are specified in the QLQ1C30, and by summing all the questions, a score (0-100) is obtained that is positively related to the quality of life of breast cancer patients.
Measured: Up to 12 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start28 Nov 2024 (estimated)
- Primary completion31 Aug 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hubei Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, HAN GUANG, Hubei Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06401005
- Sponsor's protocol ID
- HBCH-RT-2024-02
- Status last verified
- Nov 2024
- First submitted
- 30 Apr 2024
- Last updated
- 2 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open, Phase II Clinical Study of SBRT, Chemotherapy, and Cadonilimab (AK104) Neoadjuvant Therapy for Triple-negative Breast Cancer (TNBC)
- ClinicalTrials.gov ID
- NCT06401005
- Acronym / sponsor ID
- HBCH-RT-2024-02
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Hubei Cancer HospitalUniversity, hospital or other
- Study start
- 28 Nov 2024 (estimated)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 6 May 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.
Studies have indicated that the improvement in pathological complete response (pCR) is significantly correlated with triple-negative breast cancer（TNBC）patients' overall survival (OS). Patients with TNBC have poor efficacy for neoadjuvant chemotherapy. The combination of neoadjuvant therapy with immunotherapy and chemotherapy has been demonstrated to enhance the pCR rate of TNBC patients, increasing it from 45% to approximately 60%. Therefore, how to further improve the pCR rate of TNBC breast cancer became the main objective of this study. Stereotactic radiotherapy (SBRT) not only kills tumor cells directly, but also kills the distant unirradiated tumor cells by promoting the cross-initiation of tumor-specific CD8+ T cells, a phenomenon known as the abscopal effect. Our research team has recently discovered that the triple therapy model of SBRT + anti-vascular targeting + anti-PD-1 was safe and efficacious in lung cancer patients. Cadonilimab (AK104) is an PD-1/CTLA-4 bispecific antibody. In order to improve the pCR, a single-arm, open, phase II clinical study was proposed to explore the safety and efficacy of SBRT+AK104+chemotherapy, a neoadjuvant treatment modality, in the treatment of TNBC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TNBC patients | Experimental | Drug: Cadonilimab (AK104) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed ER-/PR-/HER2- invasive breast cancer patients (ER/PR immunohistochemistry negative or<1%; Her2 immunohistochemistry of 0, 1+, or 2+/FISH-) patients; patients meeting one of the following conditions: (1) tumor mass larger than 2cm, (2) the presence of axillary lymph node metastasis, and (3) the desire to conserve breasts, but the ratio of tumor size to breast volume is large and difficult to conserve breasts;
- Patients aged ≥18 years old;
- ECOG score of 0-1;
- Biochemical test indexes before enrollment must meet the following criteria, hematologic: white blood cell count (WBC) ≥ 2.0x10^9/L; neutrophil count (ANC) ≥ 1.5×10^9/L; platelet count (PLT) ≥ 100×10^9/L; hemoglobin (Hb) ≥ 90g/L; function: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); glutamate aminotransferase (ALT) ≤3 × ULN; aspartate aminotransferase (AST) ≤3 × ULN; renal function: creatinine (Cr) ≤1.5 × ULN; if >1.5 × ULN, creatinine clearance needs to be ≥50mL/min (calculated according to Cockcroft-Gault formula); coagulation: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN.
Key exclusion criteria (16 listed)
- Received chemotherapy, targeted therapy, or radiation therapy within 12 months prior to first use of study drug;
- Solid organ or blood system transplantation;
- Myocardial infarction, poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) within 6 months prior to first use of study drug (QTc intervals are calculated using the Fridericia formula, which is: QTc=QT/RR ^0.33);
- Class III-IV cardiac insufficiency according to NYHA criteria or cardiac ultrasound: LVEF < 50%;
- poorly controlled hypertension (defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg), previous hypertensive crisis or hypertensive encephalopathy;
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 |
|---|---|---|
| Cadonilimab (AK104)8Gy*3 SBRT to irradiate the primary lesion (without axillary lymph node metastasis) or 6Gy*3 SBRT irradiation to irradiate the primary lesion and axillary lymph node metastasis will be administered at first. And then the first cycle of chemotherapy+AK104 given within 24 hours of the end of SBRT. The total eight cycles of preoperative chemotherapy combined with immunotherapy were administered. Surgical resection was performed within 4-6 weeks after the completion of the eighth cycle of chemotherapy combined with immunotherapy. The chemotherapy regimen consisted of: Four cycles of doxorubicin 50mg/m2 (Q3W) + cyclophosphamide 600mg/m2 (Q3W) were administered, followed by four cycles of sequential albumin paclitaxel (125 mg/m2, d1, d8) and carboplatin (AUC=6, d1, Q3W) for 4 cycles. Postoperative completion of 9 cycles of immunotherapy was continued ± the need for postoperative adjuvant radiotherapy was confirmed based on the patient's preoperative status. | Drug | TNBC patients |
Primary outcome
Complete pathologic remission (pCR) rate
Time frame: Up to the 30 weeks
pCR is defined as ypT0/Tis and ypN0
3 secondary outcomes
Objective response rate
Time frame: Up to the 30 weeks
EFS
Time frame: Up to 12 months after surgery
Quality of life assessment
Time frame: Up to 12 months after surgery
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 2 Dec 2024.
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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 Cadonilimab (AK104) in people with Breast Cancer, run by Hubei Cancer Hospital 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 4 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 2 Dec 2024. 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 Xinjun Liang (13995607152, hbchgcp_003@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete pathologic remission (pCR) rate (time frame: Up to the 30 weeks). 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 2 Dec 2024.