Overview
Increased fibroblast activation protein expression is positively correlated with the aggressiveness of cancer. Radiolabeled fibroblast activation protein inhibitor therapy, also known as radioligand therapy has become a novel treatment for patients with refractory cancer and disease progression after multiple-lines treatment. However, a major problem in the therapeutic use of 177Lu-DOTA-FAPI has been its short half-life and fast rate of clearance. This study was designed to evaluate the safety and tolerabilityof a long-lasting radiolabeled fibroblast activation protein inhibitor 177Lu-DOTA-EB-FAPI in patients with various refractory solid tumors.
Description
This IIT study will include a maximum of 20 subjects with progressive cancer after multiple-line treatment, with an increased radiotracer uptake in tumors on 68Ga-FAPI-46 PET/CT. The fixed dose of 177Lu-DOTA-EB-FAPI is 3.3GBq (90 mCi). Treatment is planned for up to 4 cycles, and the time interval between cycles is 6 weeks. The primary endpoint assessed the safety and maximum tolerated dose of 177Lu-DOTA-EB-FAPI used for radioligand therapy in patients with various advanced tumors. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-DOTA-EB-FAPI.
Eligibility
Inclusion Criteria:
- Ability to understand and willingness to sign a written informed consent document.
- Age 18 and older.
- Confirmed unresectable or metastatic refractory cancer with measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion > 1 cm or lymph node > 1.5 cm in short axis).
- Progressive disease after multiple-lines treatment.
- Eastern Cooperative Oncology Group Performance Status ≤ 3.
- Participant must have completed prior therapy at least 2 weeks (washout period) prior to 68Ga-FAPI-46 PET/CT scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved below Grade 2 or baseline. Completion of entry into 68Ga-FAPI-46 study and completion of scan.
- Hematologic parameters defined as: Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 50,000/mm3 Hemoglobin ≥ 8 g/dL.
- Blood chemistry levels defined as: AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 3 times ULN Creatinine ≤ 3 times ULN Able to remain motionless for up to 30-60 minutes per scan.
Exclusion Criteria:
- Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA).
- Participants with Class 3 or 4 NYHA Congestive Heart Failure.
- Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding).
- Pregnant or lactating women.
- Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e. larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to study day 1 or anticipated surgery within the subsequent 6 weeks.
- Has an additional active malignancy requiring therapy within the past 2 years.
- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Psychiatric illness/social situations that would interfere with compliance with study requirements
- Cannot undergo PET/CT scanning because of weight limits (350 lbs).
- INR>1.2; PTT>5 seconds above UNL.