Evaluatioon of 177Lu-TATE-EB-01（LNC1010）in SSTR2-positive Tumors

April 14, 2024 updated by: The First Affiliated Hospital of Xiamen University

A Phase 1, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness of 177Lu-TATE-EB-01（LNC1010）in Adult Subjects With SSTR2-positive Tumors

177Lu-LNC1010(177Lu-EB-TATE-01) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs).

In this study, we designed and developed a new radioligand, EB-TATE-01 (second generation long-acting EB-TATE formula), through combining EB and altering the linker to further improve the pharmacokinetics and pharmacodynamics, leading to substantially enhanced radioligand therapy effect.

This is an open-label, non-controlled, non-randomized study to investigate the long-lasting radiolabeled somatostatin analogue based peptide receptor radionuclide therapy and evaluate response to 177Lu-LNC1010 in patients with advanced SSTR2-positive tumors. Different groups with doses of 2.22GBq (60 mCi), 3.7GBq (100mCi) and 5.18GBq (140mCi) of 177Lu-LNC1010 will be injected intravenously. All patients will undergo 68Ga-DOTA-Octreotide(TATE) PET/CT scans before and after the treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Somatostatin receptor(SSTR), especially SSTR subtype 2 (SSTR2),has been a popular target for molecular imaging and radionuclide therapy in recent years. SSTR antagonists, such as LNC1010, have emerged as a new type of somatostatin analog, characterized by a low internalization rate and high tumor affinity. 68Ga-DOTA(68Ga-DOTA)-LNC1010 has been reported that it showed favorable biodistribution, high tumor uptake, and good tumor retention, resulting in high image contrast. SSTR2 has been found highly expressed in SSTR2-positive tumors, indicating the feasibility of Positron Emission Tomography（PET)/ CT with 68Ga-DOTA-conjugated peptides for imaging SSTR2 expression and peptide-receptor radionuclide therapy (PRRT) for the treatment option in SSTR2-positive tumors. However, a major problem in the therapeutic use of 177Lu-DOTA(177Lu-DOTA)-LNC1010 has been its short half-life and fast rate of clearance. This study was designed to evaluate the efficacy of a long-lasting radiolabeled somatostatin analogue 177Lu-LNC1010 in patients with SSTR2-positive tumors.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Xiamen, China, 361000
        • Recruiting
        • The First Affiliated Hospital of Xiamen University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18 years or older;
  • Histologically proven or cytologically confirmed, inoperable, NPC, and SSTR positive cancers;
  • Measurable disease as defined by Response Criteria in Solid Tumors (RECIST) version 1.1;
  • Overexpression of somatostatin receptors of the target lesions at 68Ga-DOTA-TATE positron emission tomography (PET)/computed tomography (CT) with standard uptake value(SUV) of lesions greater than normal liver in at least 1 lesion;
  • Patients who were able to provide informed consent (signed by participant, parent or legal representative) and assent according to the guidelines of the Clinical Research Ethics Committee.

Exclusion Criteria:

  • Women who are pregnant or breastfeeding;
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-EB-TATE as assessed from medical records;
  • Previous radioligand treatment with 177Lu-DOTA-TATE;
  • Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 4 weeks or 4 half-lives whichever is longer, before the first administration of study drug;
  • Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 3 months after the last dose of study drug;
  • Life expectancy < 3 months as assessed by the treating physician;
  • Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;
  • The inability or unwillingness of the research participant, parent or legal representative to provide written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 177Lu-LNC1010 1
The patients were intravenously injected with single dose 2.22GBq (60 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
Drug: 177Lu-LNC1010 1
The patients were intravenously injected with single dose 2.22GBq (60 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
Experimental: 177Lu-LNC1010 2
The patients were intravenously injected with single dose 3.7GBq (100 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
Drug: 177Lu-LNC1010 2
The patients were intravenously injected with single dose 3.7GBq (100 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
Experimental: 177Lu-LNC1010 3
The patients were intravenously injected with single dose 5.18 GBq (140mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.
Drug: 177Lu-LNC1010 3
The patients were intravenously injected with single dose 5.18GBq (140 mCi) of 177Lu-LNC1010 and underwent 68Ga-DOTA-TATE PET/CT scans before and after the treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
68Ga-Fibroblast activation protein inhibitor 46 and 18F-fluorodeoxyglucose will be performed for efficacy evaluation by RECIST 1.1 and PERCIST. Particularly, 68Ga-FAPI-46 will be performed at baseline and beginning of each circle, and 2 weeks after the last treatment. 18F-FDG will be performed at baseline and 2 weeks after the last treatment.
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Incidence of treatment-related adverse events (safety and tolerability)
Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: baseline, every 8 weeks up to 1 year after last patient first treatment
Progression-free survival is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause.
baseline, every 8 weeks up to 1 year after last patient first treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Xiamen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2022

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

June 5, 2022

First Submitted That Met QC Criteria

June 5, 2022

First Posted (Actual)

June 8, 2022

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 14, 2024

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022KY051

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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