Clinical trial NCT04233476: 99mTc-3PRGD2 SPECT/CT for Integrin Imaging of Lung Cancer
Official title: Safety and Efficacy of 99mTc-hydrazinonicotinamide-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2) SPECT/CT for Integrin αVβ3 Imaging of Lung Cancer and Mapping Lymph Node Metastases: A Prospective Multicenter, Self-controlled, Phase 3 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Lymph Node Metastasis
Keywords: 99mTc-3PRGD2
Integrin ανβ3
lung cancer
lymph node metastasis
Lead sponsor: RDO Pharm.
Sponsor class: INDUSTRY
Collaborators: name: Beijing Pharbers Genesis Pharmaceutical Technology Co., Ltd.
First posted: 2020-01-18
Enrollment: 409
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: Inclusion criteria

Participants must meet all of the following inclusion criteria to be eligible for this study:

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.

Primary outcomes:
measure: Evaluate whether the diagnostic specicity of 99mTc-3PRGD2 SPECT/CT is superior to that of 18F-FDG PET/CT in mapping lymph node metastasis of lung cancer in the same group of patients.
timeFrame: From the informed consent of the first participant to 2 weeks after the intervention of the last participants or until the last participant accepted surgery within 2 weeks
Secondary outcomes:
measure: Diagnostic accuracy, sensitivity, positive predictive value and negative predicive value of 99mTc-3PRGD2 SPECT/CT in mapping lymph node metastasis of lung cancer, with a head-to-head comparison to 18F-FDG PET/CT.
timeFrame: From the informed consent of the first participant to 2 weeks after the intervention of the last participants or until the last participant accepted surgery within 2 weeks
measure: Efficacy of 99mTc-3PRGD2 SPECT/CT in diagnosis of lung cancer, with a head-to-head comparison to 18F-FDG PET/CT.
timeFrame: From the informed consent of the first participant to 2 weeks after the intervention of the last participants or until the last participant accepted surgery within 2 weeks
measure: Incidence of adverse events for safety evaluation of 99mTc-3PRGD2 injection and SPECT/CT imaging in human beings
timeFrame: From the informed consent of the first participant to 2 weeks after the intervention of the last participants or until the last participant accepted surgery within 2 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia Autonomous Region
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Renji Hospital of Shanghai Jiao Tong University
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical Universit
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
affiliation: Peking Union Medical College Hospital
name: Zhaohui Zhu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: