Breast NeoplasmsPhase 1/2NCT05981001
Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer
A Phase 1/2 study testing Surgery for harvesting tumor-draining lymph nodes, Cyclophosphamide and Fludarabine in people with Breast Neoplasms, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial summary
RATIONALE: Patients with HER2-negative advanced breast cancer have limited choice on targeted therapies, and often show only modest responses to available immunotherapies. Adoptive cell therapy with tumor-infiltrating lymphocytes has difficulties in preparing enough cells from solid tumors and overcoming the… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Surgery for harvesting tumor-draining lymph nodes, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2023to 30 Apr 2035
- Phase
- Phase 1/2
- 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
- In order to be eligible for participation in this trial, the participant must:
- Have signed the informed consent to study participation.
- Be a female subject and aged between 18 and 70 years.
- Have locally advanced or recurrent inoperable HER2-negative breast cancer (Stage IIIB~IIIC) which cannot be treated with curative intent OR have metastatic breast cancer (Stage IV). HER2-negative breast cancer is defined by the most recent ASCO/CAP guidelines. Participants should appear clinically stable in the opinion of the investigator.
- Participants with estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancer have failed at least one line of hormonal therapy or CDK4/6 inhibitor, or are appropriate candidates for chemotherapy. Participants with ER-positive and/or PR-positive breast cancer may have received unlimited prior chemotherapy. Participants with triple-negative breast cancer (TNBC) may have received unlimited prior treatments for breast cancer.
- Have not received the chemotherapeutic drugs and immune checkpoint inhibitor intended to be used in this study in the prior treatments for the Stage IIIB, IIIC or IV breast cancer. Participants who received the same chemotherapeutic drugs and/or immune checkpoint inhibitor in the (neo)adjuvant setting as in this study are eligible, only if ≥12 months have elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, whichever occurred last) and the enrollment of this study.
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- Have not received any prior adoptive cell therapy.
- Be suitable for treatment with nab-paclitaxel or gemcitabine/carboplatin and camrelizumab as judged by the investigator.
- Have accessible tumor-draining lymph nodes by surgery to grow LNL.
- Have measurable disease based on RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable, only if they have shown unequivocal progression based on RECIST 1.1 after radiation therapy.
- Have provided recently or newly obtained biopsy from a locally advanced or recurrent inoperable or metastatic tumor lesion for pathological examination of molecular subtype and PD-L1 expression, unless contraindicated due to site inaccessibility and/or participant safety concerns.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Have life expectancy ≥4 months.
- Demonstrate adequate normal organ function:
- NOTE: Blood component or cytokine therapy is not allowed within 14 days before surgery.
- Routine blood test:
- Absolute neutrophil count (ANC) ≥1.5×10^9/L
- Lymphocyte count (LC) >0.5×10^9/L
- Platelets (PLT) ≥100×10^9/L
- Hemoglobin (Hb) ≥90 g/L
- Liver function test:
- AST and ALT ≤2.5 ×ULN (≤5×ULN for participants with liver metastases)
- ALP ≤2.5 ×ULN (≤5×ULN for participants with liver or bone metastases)
- Total bilirubin ≤1.5×ULN (≤3.0 mg/dL for participants with Gilbert's syndrome)
- Renal function test:
- Calculated creatinine clearance (CrCL) ≥45 mL/min OR creatinine ≤1.5 × ULN
- Coagulation function test:
- APTT ≤1.5 ×ULN
- INR or PT ≤1.5×ULN
- Doppler echocardiography:
- Left ventricular ejection fraction (LVEF) ≥50%
- Pulmonary function test:
- FEV1≥60%
- Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through one year (or longer as specified by local institutional guidelines) after the last dose of study treatment. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to LNL infusion.
- Have a specified washout period from prior anticancer therapies to the enrollment:
- Angiogenesis inhibitors: 4 weeks
- Chemotherapy or targeted therapy: 3 weeks
- Radiotherapy: 2 weeks
- Hormonal therapy: one week
- Have recovered from prior therapy-related adverse events to Grade≤1 per CTCAE version 5.0 criteria or met the criteria of normal organ function specified above, except for second-degree peripheral nerve injury, alopecia, leukoderma, hypothyroidism controlled by thyroid hormone replacement therapy, type 1 diabetes controlled by insulin therapy, and other irreversible toxic events that would not be exacerbated by LNL infusion as judged by the investigator (e.g., hearing loss).
Who cannot join
- The participant must be excluded from participating in this trial if the participant:
- Has rapidly progressing tumors, as judged by the investigator.
- Has known active CNS metastases and/or carcinomatous meningitis except for previously treated and radiographically stable CNS metastases, or CNS metastases without medication requirement and corticosteroid dependence. To demonstrate radiographic stability of brain metastases, a minimum of 2 post-treatment brain imaging assessments are required: (1) The first brain imaging must be acquired after treatment of brain metastases has been completed; (2) The second brain imaging must be obtained during screening and 4 weeks after the previous post-treatment brain imaging.
- Has spinal cord compression not relieved by surgery or radiotherapy. Participants with previously treated spinal cord compression may participate provided that the compression-related symptoms are relieved within more than one week prior to surgery for tumor-draining lymph nodes.
- Has uncontrolled pleural effusion, pericardial effusion or ascites. Participants with indwelling catheter may participate.
- Has uncontrolled cancer pain as judged by the investigator. Participants requiring pain medication must have a treatment plan before enrollment. Symptomatic lesions suitable for palliative radiotherapy should be treated before enrollment.
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- Has a known additional malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, and ductal carcinoma in situ that has undergone radical mastectomy.
- Has a known history of cardiovascular disease, including but not limited to, (1) congestive heart failure (New York Heart Association [NYHA] functional classification Class > 2), (2) unstable angina pectoris, (3) myocardial infarction in the past 3 months, (4) supraventricular arrhythmia or ventricular arrhythmia that requires treatments.
- Has interstitial pneumonia or active pneumonia that has clinical implication, or other respiratory diseases that seriously affect pulmonary function.
- Has an active infection requiring systemic therapy or has an unexplained fever of >38.5℃ except fevers caused by cancer.
- Has arterial and/or venous thrombotic events in the past 5 months, e.g., cerebrovascular accident, deep vein thrombosis or pulmonary embolism.
- Is currently participating in a clinical study and receiving an investigational agent and/or using an investigational device, or has participated in a clinical study and received an investigational agent and/or used an investigational device within 4 weeks prior to enrollment.
- Note: Subjects who have entered the follow-up phase of a clinical study may participate as long as 4 weeks have elapsed since the last dose of the investigational agent and/or removal of the device.
- Has a known psychiatric, alcohol abuse or substance abuse disorders.
- Is pregnant or breastfeeding.
- Has an active autoimmune disease, a history of autoimmune disease, or autoimmune disease that has required systemic treatment (e.g., with use of prednisone at a dose of >10mg per day or other corticosteroids at an equivalent dose). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
- Has a history of congenital immunodeficiency or acquired immunodeficiency (e.g., positive serology test for HIV).
- Has tuberculosis in the past one year, or has a history of active tuberculosis more than one year but did not receive regular treatments.
- Has known active hepatitis B or hepatitis C. Participants that are hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) positive may participate provided that the HBV DNA level is normal. Participants that are hepatitis C antibody positive may participate provided that the HCV DNA level is normal. Carriers of HBV or HCV must receive anti-virus therapy, and take regular DNA copy number tests during this trial.
- Has received a live vaccine within 4 weeks prior to enrollment, or plans to receive a live vaccine during this trial.
- Has a history of allogeneic bone marrow or organ transplant.
- Has a history of hypersensitivity or allergy to the drugs in this study and any of their components including but not limited to, LNL, cyclophosphamide, fludarabine, interleukin-2, dimethyl sulphoxide (DMSO), human serum albumin (HSA), dextran-40, antibiotics (β-lactam antibiotics, gentamicin), camrelizumab, nab-paclitaxel or gemcitabine/carboplatin).
- Has contraindication for use of IL-2, including but not limited to, refractory or intractable epilepsy, and active gastrointestinal bleeding.
- Has a history of Grade≥2 neuropathy.
- Is receiving any medication prohibited in combination with study treatments as described in the respective product labels, unless medication was stopped within 7 days prior to enrollment.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or render study participation not compatible with the participant's best interest, in the opinion of the investigator.
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
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510120
Shicheng Su, M.D., Ph.D., +86 13632394954, lnl_trial@126.com
Erwei Song, M.D., Ph.D., +86 13719237746, lnl_trial@126.com
About this study
Official title: An Open-Label Phase I/II Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer
RATIONALE: Patients with HER2-negative advanced breast cancer have limited choice on targeted therapies, and often show only modest responses to available immunotherapies. Adoptive cell therapy with tumor-infiltrating lymphocytes has difficulties in preparing enough cells from solid tumors and overcoming the exhaustion and dysfunction of T cells, which limit its clinical use. Tumor-draining lymph node-derived lymphocytes (LNLs) that have abundant tumor-specific T cells, rather than exhausted T cells, are easier to produce. It is not yet known whether LNL treatment is safe and effective in patients with advanced HER2-negative breast cancer.
PURPOSE: This open-label phase I/II trial is to study the safety and efficacy of autologous LNL in patients with advanced HER2-negative breast cancer.
- Conditions
- Breast Neoplasms
- Being tested
- Surgery for harvesting tumor-draining lymph nodes, Cyclophosphamide, Fludarabine, Tumor-draining lymph node-derived lymphocyte (LNL), Interleukin-2
- Keywords
- HER2-Negative, Lymph Node, Lymphocytes, Adoptive Cell Therapy, Camrelizumab, Chemotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgery for harvesting tumor-draining lymph nodesProcedure or surgery
A sample of the participant's tumor-draining lymph nodes will be collected and sent to the biotherapy center for LNL isolation and expansion.
CyclophosphamideDrug
Cyclophosphamide will be administered at 60 mg/kg IV daily over approximately two hours for two days. Cyclophosphamide will be initiated seven days prior to the anticipated LNL transfer, and the precise timing will depend on the rate of in vitro LNL growth.
FludarabineDrug
After administration of cyclophosphamide, fludarabine will then be infused at 25 mg/m^2 intravenous piggyback (IVPB) daily over approximately 30 minutes for five days, starting five days prior to LNL transfer.
Tumor-draining lymph node-derived lymphocyte (LNL)Biological
Also called LNL
In the dose-escalation portion of phase I study, participants receive ascending dose (1×10^9~18×10^9), single Infusion of LNL on day 0. In the dose-expansion portion of phase I study, participants receive single infusion of LNL at the recommended phase 2 dose (RP2D).
In the phase II study, participants receive single infusion of LNL at the RP2D.
Interleukin-2Biological
Also called IL-2
Eight to twelve hours after completing the LNL infusion, all participants will receive intermediate-dose decrescendo IL-2 IV.
CamrelizumabBiological
Also called SHR-1210
Camrelizumab will be administered at a fixed dose of 200mg IV on Day 1 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.
Nab-paclitaxelDrug
Nab-paclitaxel will be administered at 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.
GemcitabineDrug
Gemcitabine will be administered at 1000 mg/m^2 IV on Days 1 and 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.
CarboplatinDrug
Carboplatin will be administered at area under the concentration-time curve 2 (AUC 2) IV on Days 1 and 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared.
| Study group | Role | What they receive |
|---|---|---|
| Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy | Experimental | Participants in both phase I and phase II portions receive LNL treatment, which consists of non-myeloablative lymphocyte depleting regimen of chemotherapy with cyclophosphamide and fludarabine, followed by infusion of LNL and interleukin-2. After LNL treatment, participants receive camrelizumab PLUS one of two background chemotherapy regimens at investigator's discretion: (1) nab-paclitaxel, OR (2) gemcitabine/carboplatin. Receives: Procedure: Surgery for harvesting tumor-draining lymph nodes; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Tumor-draining lymph node-derived lymphocyte (LNL); Biological: Interleukin-2; Biological: Camrelizumab; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Carboplatin |
| Phase II: Camrelizumab + Chemotherapy | Active comparator | The single-arm phase I study did not have this arm. Participants in phase II portion receive camrelizumab PLUS one of two background chemotherapy regimens at investigator's discretion: (1) nab-paclitaxel, OR (2) gemcitabine/carboplatin. Receives: Biological: Camrelizumab; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Incidence of Dose-Limiting Toxicity (DLT)
Adverse events are reported based upon Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. DLT will be defined as a non-hematologic Grade 3 or higher adverse event, occurring within the 28 days immediately after LNL infusion, that is probably or definitely related to LNL infusion, and lasts more than 28 days or does not resolve to Grade<3 despite treatment with dexamethasone at 10 mg per 12 hours IV for 7 days (or other corticosteroid at equivalent dose), and/or tocilizumab at 8mg/kg IV for three times.
Measured: From the LNL infusion up to 28 days post-infusion
Phase I: Incidence of Grade≥3 Treatment-Emergent Adverse Event (TEAE)
Adverse events are reported based upon CTCAE version 5.0 criteria. The incidence of Grade≥3 TEAE occurring within the 28 days immediately after LNL infusion will be summarized with descriptive statistics.
Measured: From the LNL infusion up to 28 days post-infusion
Phase II: Progression-Free-Survival (PFS)
Progression-free survival is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first.
Measured: Up to approximately two years
Secondary outcomes (9)
Phase I: PFS
Progression-free survival is defined as the time from enrollment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurs first.
Measured: Up to approximately two years
Phase I and phase II: Overall Survival (OS)
Overall survival is defined as the time from enrollment (phase I) or randomization (phase II) to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Measured: Up to approximately five years
Phase I and phase II: Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR) or partial response (PR). The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.
Measured: Up to approximately two years
Phase I and phase II: Disease Control Rate (DCR)
Disease control rate is defined as the percentage of participants who have achieved CR or PR or have demonstrated stable disease (SD) for at least 24 weeks, per RECIST 1.1.
Measured: Up to approximately two years
Phase I and phase II: Duration of Response (DOR)
For participants who demonstrate a confirmed CR or confirmed PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD per RECIST 1.1 or death due to any cause, whichever occurs first.
Measured: Up to approximately two years
Phase I: Levels of multiple different cytokines in blood samples before and after LNL infusion.
To evaluate the pharmacokinetics and pharmacodynamics of LNL, levels of multiple different cytokines in blood samples including Granzyme B, IFN-γ, GM-CSF, IL-2, IL-4, IL-6, etc. will be measured using cytokine chips, ELISA or flow cytometry at various time points before and after LNL infusion.
Measured: Up to approximately two years
Phase I: Distribution of T cell subsets in blood samples before and after LNL infusion.
To evaluate the pharmacokinetics and pharmacodynamics of LNL, distribution of T cell subsets in blood samples will be measured using flow cytometry at various time points before and after LNL infusion.
Measured: Up to approximately two years
Phase I: Distribution of T-cell receptor (TCR) clonotype in blood samples before and after LNL infusion.
To evaluate the pharmacokinetics and pharmacodynamics of LNL, distribution of T-cell receptor (TCR) clonotype in blood samples will be measured using TCR sequencing at various time points before and after LNL infusion.
Measured: Up to approximately two years
Phase II: Incidence of Grade≥3 Treatment-Emergent Adverse Event (TEAE)
Adverse events are reported based upon CTCAE version 5.0 criteria. The incidence of Grade≥3 TEAE occurring within the 28 days immediately after LNL infusion will be summarized with descriptive statistics.
Measured: From the LNL infusion up to 28 days post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2023
- Study start1 Aug 2023 (estimated)
- Primary completion30 Apr 2032 (estimated)
- Study completion30 Apr 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Phase I: Single-arm, dose-escalation and dose-expansion study Phase II: Two-arm parallel assignment
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erwei Song, M.D., Ph.D., Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Investigators
- Erwei Song, M.D., Ph.D., Principal investigator, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05981001
- Sponsor's protocol ID
- 【2021】03-01
- Status last verified
- Jul 2023
- First submitted
- 17 Jul 2023
- Last updated
- 8 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase I/II Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT05981001
- Acronym / sponsor ID
- 【2021】03-01
- Conditions
- Breast Neoplasms
- Keywords
- HER2-Negative, Lymph Node, Lymphocytes, Adoptive Cell Therapy, Camrelizumab, Chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Aug 2023 (estimated)
- Primary completion
- 30 Apr 2032 (estimated)
- Study completion
- 30 Apr 2035 (estimated)
- First posted
- 8 Aug 2023 (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.
RATIONALE: Patients with HER2-negative advanced breast cancer have limited choice on targeted therapies, and often show only modest responses to available immunotherapies. Adoptive cell therapy with tumor-infiltrating lymphocytes has difficulties in preparing enough cells from solid tumors and overcoming the exhaustion and dysfunction of T cells, which limit its clinical use. Tumor-draining lymph node-derived lymphocytes (LNLs) that have abundant tumor-specific T cells, rather than exhausted T cells, are easier to produce. It is not yet known whether LNL treatment is safe and effective in patients with advanced HER2-negative breast cancer.
PURPOSE: This open-label phase I/II trial is to study the safety and efficacy of autologous LNL in patients with advanced HER2-negative breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase I: Single-arm, dose-escalation and dose-expansion study Phase II: Two-arm parallel assignment
| Arm | Type | Receives |
|---|---|---|
| Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy | Experimental | Procedure: Surgery for harvesting tumor-draining lymph nodes, Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Tumor-draining lymph node-derived lymphocyte (LNL), Biological: Interleukin-2, Biological: Camrelizumab, Drug: Nab-paclitaxel, Drug: Gemcitabine, Drug: CarboplatinParticipants in both phase I and phase II portions receive LNL treatment, which consists of non-myeloablative lymphocyte depleting regimen of chemotherapy with cyclophosphamide and fludarabine, followed by infusion of LNL and interleukin-2. After LNL treatment, participants receive camrelizumab PLUS one of two background chemotherapy regimens at investigator's discretion: (1) nab-paclitaxel, OR (2) gemcitabine/carboplatin. |
| Phase II: Camrelizumab + Chemotherapy | Active comparator | Biological: Camrelizumab, Drug: Nab-paclitaxel, Drug: Gemcitabine, Drug: CarboplatinThe single-arm phase I study did not have this arm. Participants in phase II portion receive camrelizumab PLUS one of two background chemotherapy regimens at investigator's discretion: (1) nab-paclitaxel, OR (2) gemcitabine/carboplatin. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Have signed the informed consent to study participation.
- Be a female subject and aged between 18 and 70 years.
- Have locally advanced or recurrent inoperable HER2-negative breast cancer (Stage IIIB~IIIC) which cannot be treated with curative intent OR have metastatic breast cancer (Stage IV). HER2-negative breast cancer is defined by the most recent ASCO/CAP guidelines. Participants should appear clinically stable in the opinion of the investigator.
- Participants with estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancer have failed at least one line of hormonal therapy or CDK4/6 inhibitor, or are appropriate candidates for chemotherapy. Participants with ER-positive and/or PR-positive breast cancer may have received unlimited prior chemotherapy. Participants with triple-negative breast cancer (TNBC) may have received unlimited prior treatments for breast cancer.
- Have not received the chemotherapeutic drugs and immune checkpoint inhibitor intended to be used in this study in the prior treatments for the Stage IIIB, IIIC or IV breast cancer. Participants who received the same chemotherapeutic drugs and/or immune checkpoint inhibitor in the (neo)adjuvant setting as in this study are eligible, only if ≥12 months have elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, whichever occurred last) and the enrollment of this study.
Key exclusion criteria (26 listed)
- Has rapidly progressing tumors, as judged by the investigator.
- Has known active CNS metastases and/or carcinomatous meningitis except for previously treated and radiographically stable CNS metastases, or CNS metastases without medication requirement and corticosteroid dependence. To demonstrate radiographic stability of brain metastases, a minimum of 2 post-treatment brain imaging assessments are required: (1) The first brain imaging must be acquired after treatment of brain metastases has been completed; (2) The second brain imaging must be obtained during screening and 4 weeks after the previous post-treatment brain imaging.
- Has spinal cord compression not relieved by surgery or radiotherapy. Participants with previously treated spinal cord compression may participate provided that the compression-related symptoms are relieved within more than one week prior to surgery for tumor-draining lymph nodes.
- Has uncontrolled pleural effusion, pericardial effusion or ascites. Participants with indwelling catheter may participate.
- Has uncontrolled cancer pain as judged by the investigator. Participants requiring pain medication must have a treatment plan before enrollment. Symptomatic lesions suitable for palliative radiotherapy should be treated before enrollment.
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 |
|---|---|---|
| Surgery for harvesting tumor-draining lymph nodesA sample of the participant's tumor-draining lymph nodes will be collected and sent to the biotherapy center for LNL isolation and expansion. | Procedure or surgery | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy |
| CyclophosphamideCyclophosphamide will be administered at 60 mg/kg IV daily over approximately two hours for two days. Cyclophosphamide will be initiated seven days prior to the anticipated LNL transfer, and the precise timing will depend on the rate of in vitro LNL growth. | Drug | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy |
| FludarabineAfter administration of cyclophosphamide, fludarabine will then be infused at 25 mg/m^2 intravenous piggyback (IVPB) daily over approximately 30 minutes for five days, starting five days prior to LNL transfer. | Drug | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy |
| Tumor-draining lymph node-derived lymphocyte (LNL)Also: LNLIn the dose-escalation portion of phase I study, participants receive ascending dose (1×10^9~18×10^9), single Infusion of LNL on day 0. In the dose-expansion portion of phase I study, participants receive single infusion of LNL at the recommended phase 2 dose (RP2D). In the phase II study, participants receive single infusion of LNL at the RP2D. | Biological | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy |
| Interleukin-2Also: IL-2Eight to twelve hours after completing the LNL infusion, all participants will receive intermediate-dose decrescendo IL-2 IV. | Biological | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy |
| CamrelizumabAlso: SHR-1210Camrelizumab will be administered at a fixed dose of 200mg IV on Day 1 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared. | Biological | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy, Phase II: Camrelizumab + Chemotherapy |
| Nab-paclitaxelNab-paclitaxel will be administered at 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared. | Drug | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy, Phase II: Camrelizumab + Chemotherapy |
| GemcitabineGemcitabine will be administered at 1000 mg/m^2 IV on Days 1 and 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared. | Drug | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy, Phase II: Camrelizumab + Chemotherapy |
| CarboplatinCarboplatin will be administered at area under the concentration-time curve 2 (AUC 2) IV on Days 1 and 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared. | Drug | Phase I and phase II: LNL treatment + Camrelizumab + Chemotherapy, Phase II: Camrelizumab + Chemotherapy |
Primary outcome
Phase I: Incidence of Dose-Limiting Toxicity (DLT)
Time frame: From the LNL infusion up to 28 days post-infusion
Adverse events are reported based upon Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. DLT will be defined as a non-hematologic Grade 3 or higher adverse event, occurring within the 28 days immediately after LNL infusion, that is probably or definitely related to LNL infusion, and lasts more than 28 days or does not resolve to Grade<3 despite treatment with dexamethasone at 10 mg per 12 hours IV for 7 days (or other corticosteroid at equivalent dose), and/or tocilizumab at 8mg/kg IV for three times.
Phase I: Incidence of Grade≥3 Treatment-Emergent Adverse Event (TEAE)
Time frame: From the LNL infusion up to 28 days post-infusion
Adverse events are reported based upon CTCAE version 5.0 criteria. The incidence of Grade≥3 TEAE occurring within the 28 days immediately after LNL infusion will be summarized with descriptive statistics.
Phase II: Progression-Free-Survival (PFS)
Time frame: Up to approximately two years
Progression-free survival is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first.
9 secondary outcomes
Phase I: PFS
Time frame: Up to approximately two years
Phase I and phase II: Overall Survival (OS)
Time frame: Up to approximately five years
Phase I and phase II: Objective Response Rate (ORR)
Time frame: Up to approximately two years
Phase I and phase II: Disease Control Rate (DCR)
Time frame: Up to approximately two years
Phase I and phase II: Duration of Response (DOR)
Time frame: Up to approximately two years
Phase I: Levels of multiple different cytokines in blood samples before and after LNL infusion.
Time frame: Up to approximately two years
Phase I: Distribution of T cell subsets in blood samples before and after LNL infusion.
Time frame: Up to approximately two years
Phase I: Distribution of T-cell receptor (TCR) clonotype in blood samples before and after LNL infusion.
Time frame: Up to approximately two years
Phase II: Incidence of Grade≥3 Treatment-Emergent Adverse Event (TEAE)
Time frame: From the LNL infusion up to 28 days post-infusion
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 8 Aug 2023.
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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.
Erwei Song, M.D., Ph.D. principal investigator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Surgery for harvesting tumor-draining lymph nodes, Cyclophosphamide and Fludarabine in people with Breast Neoplasms, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen 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 40 inclusion and 26 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 8 Aug 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Shicheng Su, M.D., Ph.D. (+86 13632394954, lnl_trial@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Incidence of Dose-Limiting Toxicity (DLT) (time frame: From the LNL infusion up to 28 days post-infusion). The study lists 3 primary outcomes in all. 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 8 Aug 2023.