Condition 1: Triple-negative breast cancer. Condition 2: Hormone-positive, HER2-negative breast cancer. Condition 3: Triple-positive breast cancer.
Conditions
Interventions
Intervention 1: Control group: Control Group: The control group will consist of 36 patients who will receive standard routine treatments based on the recommendations of the interdisciplinary tumor boa
Sponsors
Shahid Beheshti University of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must be at least 18 years old at the time of signing the informed consent form for study participation. Adequate organ function must be confirmed based on the following laboratory results obtained during the screening period and prior to the administration of [^68Ga]Ga-FAPI-2286, as well as before the initiation of the first cycle of chemotherapy in the combination therapy group:a. Bone marrow function (independent of transfusions or growth factor support within 21 days prior to the first planned administration of [177Lu]Lu-FAPI-2286):Absolute neutrophil count (ANC) = 1.5 × 10?/LPlatelet count > 100 × 10?/LHemoglobin = 9 g/dLb. Hepatic function:ALT and AST = 3 times the upper limit of normal (ULN); in cases of hepatic metastases, = 5 times ULNSerum bilirubin = 1.5 × ULN; in participants with known Gilbert’s syndrome, = 3 × ULNSerum albumin = 30 g/L (3 g/dL)International normalized ratio (INR) = 1.5 × ULN and activated partial thromboplastin time (aPTT) = 1.5 × ULN;This criterion applies to participants not receiving therapeutic anticoagulation. Participants on anticoagulants must be on a stable dose.c. Renal function:Estimated glomerular filtration rate (eGFR) = 60 mL/min, calculated using the Cockcroft-Gault formula Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants must have a life expectancy of at least 6 months. Participants must have at least one measurable lesion according to RECIST version 1.1 criteria, meeting the following conditions:a. At least one lesion with a longest diameter = 10 mm for non-lymph node lesions or a short-axis diameter = 15 mm for lymph node lesions, which can be serially measured using conventional CT and/or MRI imaging, in accordance with RECIST version 1.1.b. Lesions previously treated with external radiotherapy or locoregional therapies such as radiofrequency ablation may be considered target lesions only if there is a clear and significant increase in size following treatment. Participants must have histologically, cytologically, and radiologically confirmed recurrent or metastatic breast cancer, meeting one of the following criteria:a. HR-positive, HER2-negative:The participant must have a documented histological and/or cytological diagnosis of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (based on the most recently analyzed tumor tissue sample in the laboratory). In addition, participants must have demonstrated resistance or disease progression after at least one line of hormonal therapy (as monotherapy or in combination with other agents) and at least one but no more than two lines of chemotherapy (including cytotoxic, targeted, and/or antibody-drug conjugates) for metastatic disease.b. HER2-positive:The participant must have a documented histological and/or cytological diagnosis of HER2-positive metastatic breast cancer (based on the most recently analyzed tumor tissue sample in the laboratory). In addition, the participant must have demonstrated resistance or disease progression after at least two lines of HER2-targeted therapy for metastatic disease.c. Triple-negative breast cancer (TNBC):The participant must have a documented histological and/or cytological diagnosis of triple-negative breast cancer (TNBC) (based on the most recently analyzed tumor tissue sample in the laboratory). In addition, participants must have demonstrated resistance or disease progression after at least two lines of cytotoxic ch
Exclusion criteria
Exclusion criteria: The presence of cutaneous local recurrence in any of the studied subtypes—HR-positive HER2-negative, HER2-positive, or triple-negative breast cancer (TNBC)—will lead to exclusion from the study. The presence of an active malignancy other than the specific type of cancer under investigation in this study will lead to exclusion. This includes participants with a known potentially life-threatening cancer, even if they are not currently undergoing treatment—except in the following cases:a. A history of a second malignancy that has been successfully treated and has shown no evidence of active disease in the past three years;b. Low-risk tumors that have been treated with surgery, such as early-stage cervical or endometrial cancer, any in situ carcinoma, or non-melanoma skin cancers;c. Previous or concurrent malignancies whose natural history or treatment does not interfere with the assessment of the safety or efficacy of the investigational treatment regimen. Symptomatic or untreated central nervous system (CNS) metastases, leptomeningeal disease, or primary CNS tumors are exclusion criteria.a. Participants with previously treated and asymptomatic CNS metastases may be eligible if they have been clinically stable for at least 4 weeks and their radiotherapy (RT) was completed more than 2 weeks prior to the start of treatment. The use of corticosteroids is permitted, provided the dose is equivalent to 10 mg of prednisone per day or less and has remained stable. Participants must not have received any anticancer treatment—including chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or investigational drugs—within 14 days prior to the administration of [177Lu]Lu-FAPI-2286. For immune checkpoint inhibitors and other antibody therapies, a minimum washout period of 28 days is required. Prior treatment with radiopharmaceuticals such as [223Ra]Ra, [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTATATE, or [225Ac]Ac-PSMA-617, or external beam radiotherapy (EBRT) involving more than 25% of the bone marrow, direct radiotherapy to the kidneys, or any form of radiotherapy within two weeks before administration is not permitted. Previous administration of any radiopharmaceutical is allowed only if at least 10 half-lives have elapsed before the administration of [68Ga]Ga-FAPI-2286. Participants must not have ongoing treatment-related adverse events of Grade 1 or higher severity according to NCI-CTCAE version 5.0, except for conditions such as alopecia or vitiligo, which are exempted. Clinically significant cardiac dysfunction or cardiovascular disease, including any of the following:a. Clinically significant and/or uncontrolled cardiac conditions such as congestive heart failure requiring treatment (greater than NYHA Class II), uncontrolled hypertension, clinically significant arrhythmias, or congenital long QT syndrome;b. Corrected QT interval (QTc), calculated using the Fridericia formula, exceeding 450 ms in men or 470 ms in women at screening;c. Acute coronary syndrome or acute myocardial infarction within 6 months prior to administration of [177Lu]Lu-FAPI-2286. Active severe urinary incontinence, significant urinary retention disorders, or urinary obstruction requiring the use of an indwelling or condom catheter, which, in the investigator’s judgment, may interfere with adherence to radiation safety protocols. Active severe or chronic HIV infection: Participants receiving effective antiretroviral therapy with an undet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Size of response to treatment. Timepoint: one month after the completion of the fourth cycle of radionuclide therapy. Method of measurement: Based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival duration of patients. Timepoint: The overall survival duration of patients will be recorded from the time of diagnosis to the date of death from any cause within one year after the completion of treatment. Method of measurement: Overall survival duration will be measured based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).;Progression-free survival duration. Timepoint: Progression-free survival will be recorded from the initial diagnosis to the date of disease progression (including regional recurrence, progression, appearance/occurrence of new metastases, or distant recurrence) or death from any cause, for a period of one year. Method of measurement: Progression-free survival will be measured based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).;Overall response rate to treatment. Timepoint: The overall response rate to treatment will be assessed one month after the fourth cycle of radionuclide therapy in all patients. Method of measurement: Overall response rate to treatment will be measured based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).;Assessment of the patient's daily physical activity after treatment. Timepoint: The patient's daily physical activity status will be evaluated one week after each cycle of radionuclide therapy. Method of measurement: Daily physical activity of the patient after treatment will be assessed using the Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Status (KPS) scale Status.;Evaluation of the patient's quality of life after treatment. Timepoint: The patient's quality of life will be assessed one week after each cycle of radionuclide therapy. Method of measurement: Patient’s quality of life after treatment will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 version 3 (EORTC QLQ-C30 v3.0).;Evaluation of the drug’s adverse effects. Timepoint: The drug's adverse effects | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactSeyede Somayyeh Banihashemian
Shahid Beheshti University of Medical Sciences
Outcome results
None listed