Advanced Malignant Solid Tumors, with a Preference for Soft Tissue Sarcoma and Ewing Sarcoma
Conditions
Interventions
Dose escalation group:68Ga-HX01 Injection (diagnostic agent): During screening, subjects receive an intravenous injection of 68Ga-HX01 at a dose of 0.07 mCi/kg (3–5 mCi per person), adjusted according
if no serious adverse reaction occurs after 42 days, the remaining two subjects are enrolled simultaneously. If =2 DLTs occur, the dose is deemed not tolerated, and the previous lower dose is designat
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. I have fully understood this study and voluntarily signed the informed consent form. 2. (1) Age must be >=18 years and =6 months; 5. Histologically or cytologically confirmed advanced malignant solid tumor. 6. Failure of prior standard therapy. 7. Positive 68Ga-HX01 PET/CT imaging. Defined as the presence of at least one lesion with SUVmax >=3.0 or a tumor-to-liver ratio (T/L ratio) >1 on 68Ga-HX01 PET/CT. 8. According to RECIST 1.1 criteria, at least one measurable tumor lesion is required. For lesions that have undergone prior radiotherapy, they can only be considered measurable if there is clear evidence of disease progression post-radiation. 9. Toxicities from prior anti-tumor therapy (e.g., chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) have recovered to =1.5×10^9/L and White blood cell count >=2.5×10^9/L; 2) Platelets >=100×10^9/L; 3) Hemoglobin >=90 g/L; (2) Liver Function: 1) Total bilirubin 30 g/L; (3) Renal Function: 1) Serum creatinine =50 mL/min; (4) Coagulation Function: 1) International Normalized Ratio (INR) <=2.0, and Activated Partial Thromboplastin Time (APTT) <=1.5 × ULN. Exception: Subjects receiving warfarin anticoagulation therapy may have an INR between 2 and <=3. 11. Women of childbearing potential must have a negative pregnancy test. Subjects (and their partners) with childbearing potential must voluntarily use effective contraception during the treatment period and for 6 months after the last dose of the investigational product, such as condoms, oral or injectable contraceptives, etc.
Exclusion criteria
Exclusion criteria: 1. Having received radiopharmaceutical therapy within 3 months prior to ^177Lu-HX02 administration, including but not limited to: Lutetium-177, Radium-223, etc. 2. Having undergone major surgery, chemotherapy, biologic therapy, immunotherapy, endocrine therapy (except hormone replacement), macromolecular targeted therapy, or unmarketed drug therapy within 4 weeks prior to ^177Lu-HX02 administration. Having received palliative localized radiotherapy, traditional Chinese medicine with anti-tumor indications, or small molecule targeted agents within 2 weeks prior to administration. 3. Having received blood transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), albumin infusion, or renal replacement therapy within 2 weeks prior to the first dose of the investigational product. 4. History, computed tomography (CT), or magnetic resonance imaging (MRI) suggests the presence of central nervous system (CNS) metastases. Exceptions: CNS metastases having received radiotherapy or surgery, no requirement for corticosteroids, anticonvulsants, or dehydrating agents to control symptoms within 2 weeks prior to the first dose, imaging indicates no progression or new brain lesions, and the subject is asymptomatic. 5. Presence of severe cardiovascular diseases, including but not limited to the following conditions: (1) Acute myocardial infarction, unstable angina, or having undergone coronary angioplasty or stenting within 6 months prior to administration; (2) New York Heart Association (NYHA) Class II to IV congestive heart failure, or left ventricular ejection fraction (LVEF) =160 mmHg and/or diastolic blood pressure >=100 mmHg despite optimal therapy); (4) Prolonged QTcF interval (>480 ms) on baseline electrocardiogram. 6. Currently having an active infection requiring systemic anti-infective therapy (e.g., acute bacterial infection, tuberculosis, active hepatitis B/C, active syphilis, etc.). Active hepatitis B is defined as: Positive HBsAg or HBcAb test results (or outside the normal reference range) accompanied by a hepatitis B viral load >2500 copies/mL or 500 IU/mL (except for subjects who have received anti-HBV therapy for at least 14 days prior to the first dose, have HBV-DNA reduced to <=2500 copies/mL or 500 IU/mL, and agree to continue treatment during the study); Active hepatitis C is defined as: Positive hepatitis C antibody (or outside the normal reference range) and positive HCV-RNA; Positive Treponema pallidum specific antibody; Positive HIV antibody. 7. Non-infectious pneumonitis requiring corticosteroid treatment and radiation pneumonitis, thrombotic events causing hemodynamic alterations, presence of active bleeding events, or other severe comorbidities. 8. Diagnosis of any other active malignancy within 5 years prior to ^177Lu-HX02 administration, except for adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, localized prostate cancer, carcinoma in situ of the cervix, or other carcinoma in situ with curative resection and no evidence of recurrence. 9. Known allergy or hypersensitivity to any component of the investigational product or its analogues. 10. Subjects with dysuria or urinary incontinence from any cause. 11. Presence of claustrophobia or other conditions that would preclude cooperation with PET/CT or SPECT/CT imaging.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events (AE), vital signs, physical examination, 12-lead electrocardiogram, and laboratory tests, etc.;Incidence rate of dose-limiting toxicities.;Exploration of the maximum tolerated dose and determination of the Recommended Phase 2 Dose?/subsequent recommended dose.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Biodistribution and radiation dosimetry;Pharmacokinetics:;Efficacy assessment: Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) based on RECIST 1.1 criteria, along with changes in tumor burden SUV on 68Ga-HX01 PET/CT imaging.; | — |
Countries
China
Contacts
Public ContactLan Xiaoli
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed