solid tumor
Conditions
Interventions
Lutetium [177Lu]-FAP-75 treatment group:Lutetium [177Lu]-FAP-75 accumulates at the tumor site, and beta rays act on surrounding tumor cells, causing tumor cell apoptosis.
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in the clinical trial, understand the research procedure and be able to sign the informed consent in person; 2. Age 18-80 years old (including 18 and 80 years old), gender is not limited; 3. ECOG score 0-1; 4. The expected survival period is not less than 4 months; 5. Subjects with solid tumors diagnosed histologically or cytologically at advanced stage (unresectable or metastatic) after failure of standard treatment (disease progression or intolerance) or lack of effective treatment are enrolled in this study. Subjects with the following tumor species are preferentially included: ·Pancreatic cancer: histologically or cytologically confirmed pancreatic ductal adenocarcinoma. Participants must have received at least one treatment regimen for unresectable locally advanced or metastatic disease, disease progression or toxic intolerance during or after treatment. ·Medullary thyroid cancer: Subjects with a confirmed histological or cytological diagnosis of medullary thyroid cancer. Subjects were treated with at least a tyrosine kinase inhibitor (TKI) in the unresectable locally advanced or metastatic stage of disease, disease progression or toxic intolerance during or after treatment. ·Soft tissue sarcoma: Subjects with histologically or cytologically confirmed soft tissue sarcoma (except chordoma). Participants had received at least one treatment regimen for unresectable locally advanced or metastatic disease, disease progression or toxic intolerance during or after treatment. 6. There must be at least one measurable target lesion (according to RECIST V1.1); The target lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area can also be selected as a target lesion if it is confirmed to have progressed and meets the RECIST V1.1 standard); 7. Positive lesion uptake in FAP PET/CT imaging (see Image Manual for the definition of positive); 8. The level of vital organ function meets the following requirements (no blood components and cell growth factors are allowed within 2 weeks before the start of the study treatment) : • Neutrophil >=1.5×10^9/L; • Platelets >=100×10^9/L; • Hemoglobin >=90g/L; • Total bilirubin =30g/L; • Serum creatinine =60 ml/min (calculated according to Cockcroft-Gault formula); • INR<=1.5×ULN and APTT<=1.5×ULN (for subjects not receiving anticoagulant therapy, stable therapy dose is required for subjects receiving anticoagulant therapy). 9. Women of childbearing age must undergo a blood pregnancy test within 72 hours before the first dosing, must be non-lactating, and must be willing to use a highly effective method of contraception during the trial period and for 7 months after the end of treatment. For men, consent should be given to use a highly effective method of contraception or have been surgically sterilized during the study period and for 4 months after the end of treatment.
Exclusion criteria
Exclusion criteria: 1. Known significant weight loss (> 10%) within 28 days prior to signing the informed consent. 2. Prior and follow-up treatment: a) Received any radionuclide therapy or radiotherapy within 6 months before enrollment. b) Prior treatment with any FAP target nuclide. c) Received anti-tumor therapy such as surgery (except diagnostic biopsy and drainage of serosal effusion), chemotherapy, immunotherapy, and monoclonal antibodies within 4 weeks prior to admission; received anti-tumor endocrine drugs within 2 weeks; received nitrosourea or mitomycin chemotherapy within 6 weeks; eluted oral targeted therapy drugs with less than 5 half-lives or 4 weeks (whichever is shorter). d) Received any other investigational drug treatment within 4 weeks prior to enrollment. e) Any surgical procedures requiring general anesthesia and significant incisions (e.g., central venous access, percutaneous feeding tube insertion) within 6 weeks of enrollment (expected surgery). 3. Combined with the following diseases: a) Patients with meningeal metastasis or diffuse central nervous system metastasis or active central nervous system metastasis who require any radiotherapy, gamma knife, surgery, or medication (including steroids, anticonvulsants, etc.) to control the symptoms of metastasis 1 month prior to screening are excluded. Patients with a limited number of stable central nervous system metastases (clinically stable for at least 4 weeks, with 3 or less metastases) could be enrolled. b) severe urinary incontinence, hydronephrosis, and severe urination dysfunction. Note: Subjects with bladder outflow tract obstruction that can be controlled with the best available standard of care (including urinal pad, drainage, etc.) are eligible for study participation. c) Co-active hepatitis B (HBV DNA>=2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the lower limit of assay). (Subjects receiving antivirals should be treated for > 2 weeks prior to enrollment.) d) Known to have acquired immune deficiency syndrome (AIDS) or tested positive for HIV. e) Active syphilis infection. 4. Known allergy to components of the investigatory drug or its analogues. 5. Malignancies outside the target tumor species that are expected to alter life expectancy or may interfere with disease assessment within the first 5 years of enrollment. The exception is for cured malignancies with a low risk of metastasis and death (5-year survival >90%), such as non-metastatic skin basal cell carcinoma or skin superficial squamous cell carcinoma. 6. Serious infections (CTCAE > Grade 2) occurred within 4 weeks prior to enrollment, such as severe pneumonia requiring hospitalization, bacteremia, infection complications, etc., and signs and symptoms of infection within 2 weeks prior to enrollment requiring intravenous antibiotic treatment (except for prophylactic antibiotic use). 7. The patient was judged by the investigator to have not recovered from an adverse event of prior treatment before first use of the investigated drug (NCI-CTC AE 5.0 rating > Grade 1); Note: Except for subjects with <= grade 2 peripheral neuropathy, hair loss, or frequent urination, if subjects have undergone major surgery, the toxic effects and/or complications of their surgical intervention must be fully recovered before starting treatment. 8. Have clinical symptoms or diseases of heart that are not well controlled, such as: (1) NYHA grade 2 and above heart failure; (2) Unstab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety index;Dose Limiting Toxicity;Second-stage dose;Overall response rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic index;Radiation dosimetry;Disease control rate (DCR);Duration of response (DoR);Progression-free survival (PFS);Overall survival (OS); | — |
Countries
China
Contacts
Public ContactYu Xianjun
Fudan University Shanghai Cancer Center
Outcome results
None listed