A Study to Evaluate the Safety and Efficacy of PRRT With 177Lu-EB-FAPI in Patients With Advanced Cholopancreatic Tumors

Study Overview
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Brief Summary
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This study is a prospective, single-center, open, single-arm, exploratory study to evaluate the safety and efficacy of 177Lu-EB-FAPI PRRT, and to explore 177Lu-EB-FAPI in patients with advanced pancreatic cancer and cholangiocarcinoma. Eligible patients with advanced pancreatic cancer or cholangiocarcinoma were screened and enrolled after signing the informed consent forms. In the first stage of the enrolled patients, the 177Lu-EB-FAPI treatment dose was determined using a 3 + 3 dose escalation mode. Patients enrolled in the second phase, divided into pancreatic cancer cohort and cholangiocarcinoma based on pathology, will receive the first phase determined dose of 177Lu-EB-FAPI every 4 weeks, and each patient will receive no more than 4 cycles. The aim of the study is to evaluate the safety and efficacy of the 177Lu-EB-FAPI treatment.

Detailed Description
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This study is a prospective, single-center, open, single-arm, exploratory study to evaluate the safety and efficacy of 177Lu-EB-FAPI PRRT, and to explore 177Lu-EB-FAPI in patients with advanced pancreatic cancer and cholangiocarcinoma. Eligible patients with advanced pancreatic cancer or cholangiocarcinoma were screened and enrolled after signing the informed consent forms. In the first stage of the enrolled patients, the 177Lu-EB-FAPI treatment dose was determined using a 3 + 3 dose escalation mode. Patients enrolled in the second phase, divided into pancreatic cancer cohort and cholangiocarcinoma based on pathology, will receive the first phase determined dose of 177Lu-EB-FAPI every 4 weeks, and each patient will receive no more than 4 cycles. The aim of the study is to evaluate the safety and efficacy of the 177Lu-EB-FAPI treatment.

Official Title
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An Exploratory Study to Evaluate the Safety and Efficacy of Peptide Receptor Radionuclide Therapy With 177Lu-EB-FAPI in Patients With Advanced Cholopancreatic Tumors

Conditions
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Advanced Pancreatic Cancer and Cholangiocarcinoma

Intervention / Treatment
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* Drug: PRRT with 177Lu-EB-FAPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the informed consent form; Age: 18-75 years old (when signing the informed consent form); Received 68 Ga-FAPI 46 PET imaging positive before treatment; Phase Ia requires patients who have previously failed at least 2 lines of systemic chemotherapy or who the investigator considers unsuitable to receive systemic chemotherapy; Phase Ib Cohort 1, enrollment of patients with hist-or cytologically confirmed metastatic pancreatic cancer; Phase Ib Cohort 2, enrollment of patients with hist-or cytologically confirmed metastatic cholangiocarcinoma; Phase Ia requires at least one evaluable lesion confirmed per RECIST 1.1 criteria; Phase Ib requires at least one measurable lesion confirmed per RECIST 1.1 criteria; ECOG score 0-1, expected survival greater than 3 months; Major organs function well; Patients must have reliable contraception during the study and within 6 months after the study period; negative serum pregnancy / urine pregnancy test within 7 days before study enrollment and must be non-lactating subjects; male subjects should agree to have contraception during the study and within 6 months after the end of the study period. Exclusion Criteria: Prior treatment before the first dose included chemotherapy and targeted therapy with any associated toxicity (CTCAE v5.0) of> 1 N. A., excluding alopecia; Severe organ failure, such as respiratory failure, uncontrolled thyroid dysfunction including hyperthyroidism and hypothyroidism, or uncorrection of K +, Na +, Ca 2 + electrolyte disorders; Within 5 years, the patient had previous or both other malignant tumors (except for cured skin basal cell carcinoma and cervical carcinoma in situ); had other malignant tumors, but the following two conditions can be enrolled: other malignant tumors treated with single surgery with R0 resection and no recurrence and metastasis; cured cervical carcinoma in situ, skin basal cell carcinoma, nasopharyngeal carcinoma and superficial bladder tumor [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)]; Major surgical treatment with significant traumatic injury within 28 days prior to the first medication; Long-term non-healed wound or fracture; Active bleeding or high risk of bleeding considered by the investigator, such as gastric fundus varices, hemoptysis, etc.; Motor / venous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, occurred within 6 months before the first medication; Patients with a history of psychiatric substance abuse and unable to quit or with mental disorders; Symptomatic interstitial lung disease, and conditions that may cause drug pulmonary toxicity or associated pneumonia; Patients with any severe and / or uncontrolled disease. Previous history of severe allergy to macromolecular drugs, or allergy to the known component of 177Lu-EB-FAPI injection; Claustrophobic or radiologically phobic patients, or patients with mental disorders or primary affective disorders; According to the discretion of the investigator, subjects with a serious hazard to subject safety or concomitant illness affecting the study or other reasons for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase Ia: Dose escalation<br>To determine the therapeutic dose of 177Lu-EB-FAPI using a 3 + 3 dose-escalation mode | Drug: PRRT with 177Lu-EB-FAPI<br>* PRRT with 177Lu-Fibroblast activation protein inhibitor and modified by Evans blue<br>|
| Experimental: Phase Ib: Dose expansion-pancreatic cancer cohort<br>In pancreatic cancer cohort, patients will receive the first phase determined dose of 177Lu-EB-FAPI every 4 weeks, and each patient will receive no more than 4 cycles. | Drug: PRRT with 177Lu-EB-FAPI<br>* PRRT with 177Lu-Fibroblast activation protein inhibitor and modified by Evans blue<br>|
| Experimental: Phase Ib: Dose expansion-cholangiocarcinoma cohort<br>In cholangiocarcinoma cohort, patients will receive the first phase determined dose of 177Lu-EB-FAPI every 4 weeks, and each patient will receive no more than 4 cycles. | Drug: PRRT with 177Lu-EB-FAPI<br>* PRRT with 177Lu-Fibroblast activation protein inhibitor and modified by Evans blue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of treatment：hematotoxicity | Safety evaluation，Complete Blood Count was done continuously during treatment by using CTCAE 5.0 during study | Up to 2 years. | 
| Objective reponse rate (ORR) | The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during phase Ib | Up to 2 years | 
| Safety of treatment：Hepatotoxicity | Safety evaluation，liver function lab test was done continuously during treatment and the level of serum ALT, AST, and total bilirubin will be evaluated by using CTCAE 5.0 during study. | Up to 2 years. | 
| Safety of treatment：renal toxicity | Safety evaluation，renal function lab test was done continuously during treatment and the level of serum creatinine will be evaluated by using CTCAE 5.0 during study. | Up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | The proportion of patients who had tumor evaluated as PR or SD according to RECIST1.1 criteria during phase Ib | Up to 2 years | 
| Duration of remission （DoR） | The time from the first assessment of the tumor as CR or PR to the first assessment of PD or death from any cause during phase Ib | Up to 2 years | 
| Progression-free survival （PFS） | The time from enrolled to disease pregression or death from any cause during phase Ib | Up to 2 years | 
| Overall survival (OS) | The time from enrolled to death from any cause during phase Ib | Up to 2 years |