68Ga-NY104 PET/CT in Von Hippel-Lindau Disease

NCT ID: NCT05810246

Last Updated: 2023-05-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2025-12-31

Brief Summary

This is a prospective, single-center, single-arm, diagnostic phase 2 study in patients with von Hippel-Lindau disease. VHL disease is a rare syndrome characterized by VHL gene mutation and HIF activation. Although genetic testing is available, the manifestations of the syndrome are protean; therefore, imaging plays a crucial role in the identification of abnormalities and subsequent follow-up of lesions. For now, conventional imaging serves as the main radiologic modality in the characterization of VHL disease. In this study, we aim to evaluate the sensitivity of 68Ga-NY104 PET/CT in patients with VHL disease. 68Ga-NY104 is a novel small molecule PET tracer targeting carbonic anhydrase IX, which is a down-streaming target of HIF and overexpressed in HIF activation. 68Ga-NY104 PET/CT is likely to function as a sensitive imaging tool to identify VHL-related tumors and to impact patient management if additional lesions are identified.

The hypotheses of this study are that

• 68Ga-NY104 PET/CT can be used as an effective imaging modality in VHL syndrome with high sensitivity
• 68Ga-NY104 PET/CT may detect lesions that are missed on conventional imaging and can result in management impact.

A total of 19 patients will be recruited at Peking Union Medical College Hospital. As an exploratory end-point, a 68Ga-NODAGA-LM3 PET/CT sub-study will be performed in patients with evidence of neuroendocrine tumors.

Detailed Description

Hypothesis

The hypotheses of this study are that

• 68Ga-NY104 PET/CT can be used as an effective imaging modality in VHL syndrome with high sensitivity
• 68Ga-NY104 PET/CT may detect lesions that are missed on conventional imaging and can result in management impact.

Objectives

Primary objective 1. To determine the sensitivity of 68Ga-NY104 PET/CT using conventional imaging as reference.

Secondary objectives

1. To determine the incremental management impact of 68Ga-NY104 PET/CT

2. To assess the interobserver agreement of 68Ga-NY104 PET/CT by comparing the two blinded independent readings

Exploratory objective

1. To compare the per-patient, per-region, and per-lesion sensitivity of 68Ga-NY104 PET/CT to 68Ga-NODAGA-LM3 PET/CT in an exploratory endpoint

Endpoints

Primary endpoint 1. Per-patient, per-region, and per-lesion positive rate of 68Ga-NY104 using conventional imaging as ground truth.

Secondary endpoints

1. Incremental impact of 68Ga-NY104 PET/CT on choice of management, defined as a decision to alter the original plan of treatment (based on conventional imaging) after considering the result of 68Ga-NY104 PET/CT (Impact is categorized as high, medium, low or no incremental impact.)

2. Observer agreement in interpretation of 68Ga-NY104 PET/CT between the two independent nuclear medicine readers.

Exploratory endpoints

1. Per-patient, per-region, and per-lesion positive rate of 68Ga-NODAGA-LM3 using conventional imaging as ground truth.

Conditions

Von Hippel-Lindau Disease

Study Design

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

Study Groups

Diagnostic imaging arm

68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis 68Ga-NODAGA-LM3 PET/CT (exploratory)

Group Type: EXPERIMENTAL

68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis) 68Ga-NODAGA-LM3 PET/CT (exploratory)

Intervention Type: DIAGNOSTIC_TEST

68Ga-NY104 PET/CT is expected to be completed within 21 days following screening. Participants will be administered a single, intravenous bolus of 68Ga-NY104 (1.8-2.2 MBq per kilogram bodyweight). PET/CT scanning will occur at 45 -75 minutes following injection of 68Ga-NY104.

Conventional imaging should be performed within one month from 68Ga-NY104 PET/CT. It includes contrast-enhanced MRI of brain and contrast-enhanced CT of abdomen and pelvis.

68Ga-NODAGA-LM3 PET/CT is optional in patients with evidence of or in suspicion of pheochromocytoma, paraganglioma, or pancreatic neuroendocrine tumor. They are encouraged to undergo exploratory 68Ga-NODAGA-LM3 PET/CT for better evaluation of neuroendocrine tumors. The decision, however, is up to the participants. 68Ga-NODAGA-LM3 PET/CT should be performed within one month after 68Ga-NY104 PET/CT. The details of 68Ga-NODAGA-LM3 PET/CT are similar to 68Ga-NY104 PET/CT.

Interventions

68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis) 68Ga-NODAGA-LM3 PET/CT (exploratory)

68Ga-NY104 PET/CT is expected to be completed within 21 days following screening. Participants will be administered a single, intravenous bolus of 68Ga-NY104 (1.8-2.2 MBq per kilogram bodyweight). PET/CT scanning will occur at 45 -75 minutes following injection of 68Ga-NY104.

Conventional imaging should be performed within one month from 68Ga-NY104 PET/CT. It includes contrast-enhanced MRI of brain and contrast-enhanced CT of abdomen and pelvis.

68Ga-NODAGA-LM3 PET/CT is optional in patients with evidence of or in suspicion of pheochromocytoma, paraganglioma, or pancreatic neuroendocrine tumor. They are encouraged to undergo exploratory 68Ga-NODAGA-LM3 PET/CT for better evaluation of neuroendocrine tumors. The decision, however, is up to the participants. 68Ga-NODAGA-LM3 PET/CT should be performed within one month after 68Ga-NY104 PET/CT. The details of 68Ga-NODAGA-LM3 PET/CT are similar to 68Ga-NY104 PET/CT.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of VHL disease, according to 2022 CSCO guideline, if any one of the following criteria is met: germline VHL alteration, family history of VHL syndrome as well as presence of at least one VHL related tumor (including hemangioblastoma, clear cell renal cell tumor, pheochromocytoma, paraganglioma, pancreatic neuroendocrine tumor, etc.), two or more hemangioblastoma, hemangioblastoma and pheochromocytoma, hemangioblastoma and clear cell renal cell tumor.

2. Age ≥ 18 y

3. Written informed consent provided for participation in the trial

4. In the opinion of investigator, willing and able to comply with required study procedures.

Exclusion Criteria

1. Patients on VEGF TKI treatment < 1 week before 68Ga-NY104 PET/CT. TKI is known to affect girentuximab binding in patients with ccRCC and is expected to have the same effect on 68Ga-NY104. If patients were on VEGF TKI treatment, such as sunitinib, sorafenib, cabozantinib, pazopanib, or lenvatinib, a washout of one week before 68Ga-NY104 PET/CT is required.

2. Patients on HIF antagonist treatment < 3 months before 68Ga-NY104 PET/CT. CA9, which encodes carbonic anhydrase IX (CAIX), is one of the genes most strongly upregulated by HIF-1. HIF antagonist, such as Belzutifan, might affect the expression of CAIX and thus the binding of 68Ga-NY104 to tumor. Withdraw of at least 3 months is required for HIF antagonist.

3. Patients with known allergic reaction to CT or MR contrast medium.

4. Patients with renal dysfunction

5. Pregnancy or breastfeeding.

6. Severe claustrophobia.

7. If the patient will undergo an exploratory 68Ga-NODGA-LM3 PET/CT and is on cold somatostatin analogue (such as Octreotide and Lanreotide), the 68Ga-NODGA-LM3 should be injected at least 24 hours after cold somatostatin analogue injection. Patients violating this criteria will not be able to attend the exploratory 68Ga-NODGA-LM3 PET/CT study but will still be considered eligible for the main study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Huo, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Uion Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Li Huo, MD

Role: CONTACT

huoli@pumch.cn

18612672038

Wenjia Zhu, MD

Role: CONTACT

zhuwenjia_pumc@163.com

18614080164

Facility Contacts

Wenjia Zhu, MD

Role: primary

zhuwenjia_pumc@163.com

Other Identifiers

NYCOV

Identifier Type: -

Identifier Source: org_study_id