99mTc-3PRGD2 SPECT/CT for Integrin Imaging of Lung Cancer

NCT ID: NCT04233476

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 409 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-12
• Study Completion Date: 2021-05-08

Brief Summary

This is a prospective, multicenter, self-controlled phase 3 clinical trial designed to evaluate the safety and efficacy of an integrin αVβ3-targeted imaging, 99mTc-3PRGD2 SPECT/CT, for diagnosis of lung cancer and mapping the lymph node metastases. The pathological results will be considered as the gold standard and the conventional metabolic imaging by 18F-FDG PET/CT will be used for a head-to-head comparison. The primary objective of this study is to evaluate the efficacy of 99mTc-3PRGD2 SPECT/CT in mapping of lymph node metastasis according to the nodal mapping system released by the International Association for the Study of Lung Cancer in 2009 (IASLC-2009). The secondary objectives include evaluation of 99mTc-3PRGD2 SPECT/CT in detection of lung cancer and the safety of 99mTc-3PRGD2 injection in human beings.

Detailed Description

Accurate evaluation of lymph node metastasis plays a pivotal role in optimizing the surgical intervention and other precision treatments for lung cancer. CT-based nodal staging of lung cancer has limitation due to its low sensitivity, which relies on variations in tumor's size and structure. 18F-FDG PET/CT demonstrates low specificity owing to the nonspecific uptake in inflammatory lymph nodes, typically necessitating additional invasive mediastinal staging. Integrin αVβ3-targeted imaging could potentially bridge this existing technical gap. As a member of integrin family, integrin αVβ3 plays a crucial role in mediating tumor formation, invasion, metastasis, and angiogenesis. Therefore, integrin αVβ3 is an attractive target for tumor diagnosis and therapy. However, as of today, no drug has been approved for either diagnosis or therapy by targeting integrin αVβ3.

A diagnostic drug targeting integrin αvβ3, technetium-99m [99mTc] labeled hydrazinonicotinamide-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2), has been developed for imaging of lung cancer and other tumors via single photon emission computed tomography/ X-ray computed tomography (SPECT/CT). After intravenous injection into the body, 99mTc-3PRGD2 is expected to be specifically taken up by integrin αVβ3-positive tumors. The images obtained by SPECT/CT will be used for diagnosis and evaluation of the tumors, thereby guiding the individualized treatments including surgical intervention.

A prospective, multicenter, self-controlled phase 3 clinical trial is designed to evaluate the safety and efficacy of an integrin αVβ3-targeted imaging, 99mTc-3PRGD2 SPECT/CT, for diagnosis of lung cancer, with mapping the lymph node metastases as the primary objective. The secondary objectives include evaluation of 99mTc-3PRGD2 SPECT/CT in detection of lung cancer and the safety of 99mTc-3PRGD2 injection in human beings. The pathological results will be considered as the gold standard and the conventional metabolic imaging by 18F-FDG PET/CT will be used for a head-to-head comparison.

More than 400 patients with suspected lung cancer are designed to be recruited from 11 medical centers. Participants who meet the inclusion and exclusion criteria will be recruited to undergo SPECT/CT planar scan and chest tomography after intravenous injection of 99mTc-3PRGD2 at a dose of 0.3 mCi/kg. They will also undergo 18F-FDG PET/CT within a week. Among them, the patients who successfully complete safety tests are included into the safety analysis set.

At least 270 participants are expected to undergo lung lobectomy and lymph node station resection within 2 weeks after the 99mTc-3PRGD2 SPECT/CT. Their pathological results will be collected and used as the gold standard to evaluate the diagnostic efficacy of 99mTc-3PRGD2 SPECT/CT for diagnosis of lung tumors and lymph node metastases, with a head-to-head comparison with 18F-FDG PET/CT. Those patients who undergo lung surgery and lymph node resection within two weeks after the 99mTc-3PRGD2 SPECT/CT will be included into the efficacy analysis set to evaluate the efficacy of the imaging method in diagnosis of lung cancer and mapping the lymph node metastases.

Conditions

Lung Cancer; Lymph Node Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

99mTc-3PRGD2 injection for SPECT/CT imaging, with 18F-FDG PET/CT for head-to-head comparison.

Participants will receive a single-dose intravenous injection of 99mTc-3PRGD2 at a dosage of approximate 11.10 MBq (0.30 mCi) per kilogram body weight. Whole-body planar scan and chest SPECT/CT imaging will be performed 40-50 min later. Chest low-dose spiral CT (120 kV, 50 mAs) will be used for attenuation correction and anatomical localization.

The conventional metabolic imaging by 18F-FDG PET/CT of the same patients within one week will be used for a self-controlled head-to-head comparison.

Group Type: EXPERIMENTAL

99mTc-3PRGD2 injection

Intervention Type: DRUG

A diagnostic drug targeting integrin αvβ3, technetium-99m \[99mTc\] labeled hydrazinonicotinamide-PEG4-E\[PEG4-c(RGDfk)\]2 (99mTc-3PRGD2), will be intravenously injected to the participants for imaging of lung cancer and mapping lymph node metastasis via single photon emission computed tomography/ X-ray computed tomography (SPECT/CT) .

Interventions

99mTc-3PRGD2 injection

A diagnostic drug targeting integrin αvβ3, technetium-99m \[99mTc\] labeled hydrazinonicotinamide-PEG4-E\[PEG4-c(RGDfk)\]2 (99mTc-3PRGD2), will be intravenously injected to the participants for imaging of lung cancer and mapping lymph node metastasis via single photon emission computed tomography/ X-ray computed tomography (SPECT/CT) .

Intervention Type: DRUG

Other Intervention Names

Technetium-99m [99mTc] labeled hydrazinonicotinamide-PEG4-E[PEG4-c(RGDfk)]2

Eligibility Criteria

Inclusion Criteria

1. Voluntarily participate and sign the Informed Consent Form;

2. Age ≥18 years old;

3. Diagnostic CT shows that the longest diameter of the tumor occupying the lung is ≥1.5 cm and the shortest diameter is ≥1.0 cm;

4. 18F-FDG PET/CT examination shows tumor occupancy in the lungs, with positive hilar and/or mediastinal lymph nodes on either enhanced CT or 18F-FDG PET/CT;

5. Willing and be able to follow scheduled visits, treatment plans, and laboratory tests;

6. Clinical laboratory examination and other indicators are within the normal range or abnormal but do not affect related examinations and treatments.

Exclusion Criteria

Patients who have any of the following are not eligible for enrollment:

1. Female patients who plan of pregnant within 6 months, or in pregnant or lactating;

2. Allergic to the test drugs, have allergic constitution, or are allergic to multiple drugs;

3. Contrast-enhanced CT examination shows ground-glass nodules without solid components;

4. Before injecting 18F-FDG, the fasting blood glucose level exceeds 7.0 mmol/L (tested by rapid blood glucose meter);

5. Body weight exceeds 100 kg;

6. With claustrophobia;

7. Cannot tolerate raising their arms and lying on the scanner bed for 15-30 min;

8. Those the investigator believes not suitable to participate in this clinical trial;

9. Those who are currently participating in another clinical trial or have participated in other clinical trials within the past 3 month.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Pharbers Genesis Pharmaceutical Technology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

RDO Pharm.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhaohui Zhu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, China

China-Japan Union Hospital of Jilin University

Changchun, Jilin, China

Shengjing Hospital of China Medical University

Shengyang, Liaoning, China

Renji Hospital of Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

First Hospital of Shanxi Medical Universit

Taiyuan, Shanxi, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Countries

China

Other Identifiers

FSRDA201901

Identifier Type: -

Identifier Source: org_study_id