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

NCT05810246 | Unknown Phase 2

• 1 other identifier: NYCOV
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Von Hippel-Lindau Disease

Outcome Measures

Primary Outcomes (8)

• Binary reading of lesions identified on 68Ga-NY104 PET/CT

  Define lesion as PET positive or PET negative lsion

  From study completion to 1 month after completion

• The number of (68Ga-NY104) PET positive lesions

  Count the number of lesions (if more than 10, record it as \>10)

  From study completion to 1 month after completion

• The number of (68Ga-NY104) PET positive regions

  Any region with at least one (68Ga-NY104) PET positive lesion is considered (68Ga-NY104) PET positive VHL-related region

  From study completion to 1 month after completion

• The number of (68Ga-NY104) PET positive patients

  Any patient with at least one (68Ga-NY104) PET positive lesion is considered (68Ga-NY104) PET positive VHL-related patient

  From study completion to 1 month after completion

• Scoring of lesions identified on conventional imaging as very unlikely / unlikely / indeterminate / likely / very likely (score 1-5)

  The likelihood of VHL-related neoplasm will be rated combining all imaging features available, including enhancement pattern, typical location, and solitary or multicentric or bilateral distribution.

  From study completion to 1 month after completion

• The number of conventional imaging positive lesions

  Count the number of lesions (if more than 10, record it as \>10)

  From study completion to 1 month after completion

• The number of conventional imaging positive regions

  Any region with at least one conventional-imaging positive VHL-related lesion is considered conventional-imaging positive VHL-related region

  From study completion to 1 month after completion

• The number of conventional imaging positive patients

  Any patient with at least one conventional-imaging positive VHL-related lesion is considered conventional-imaging positive VHL-related patient

  From study completion to 1 month after completion

Secondary Outcomes (4)

• The intent of initial management plan (Plan 1) based on conventional imaging

  From study completion to 1 month after completion

• The intent of post-PET management plan (Plan 2) based on all information available, including the results of conventional imaging, 68Ga-NY104 PET/CT, and additional confirmatory studies.

  From study completion to 1 month after completion

• The specified management plan of initial management plan (Plan 1) based on conventional imaging

  From study completion to 1 month after completion

• The specified management plan of post-PET management plan (Plan 2) based on all information available, including the results of conventional imaging, 68Ga-NY104 PET/CT, and additional confirmatory studies.

  From study completion to 1 month after completion

Other Outcomes (4)

• Binary reading of lesions identified on 68Ga-NODAGA-LM3 PET/CT as PET positive lesions or PET negative lesions

  From study completion to 1 month after completion

• The number of (68Ga-NODAGA-LM3) PET positive lesions

  From study completion to 1 month after completion

• The number of (68Ga-NODAGA-LM3) PET positive regions

  From study completion to 1 month after completion

Study Arms (1)

Diagnostic imaging arm

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)

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

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) 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.

Diagnostic imaging arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 y
• Written informed consent provided for participation in the trial
• In the opinion of investigator, willing and able to comply with required study procedures.

You may not qualify if:

• 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.
• 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.
• Patients with known allergic reaction to CT or MR contrast medium.
• Patients with renal dysfunction
• Pregnancy or breastfeeding.
• Severe claustrophobia.
• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

von Hippel-Lindau Disease

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Li Huo, MD

  Peking Uion Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Huo, MD

CONTACT

18612672038; huoli@pumch.cn

Wenjia Zhu, MD

CONTACT

18614080164; zhuwenjia_pumc@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: April 12, 2023
• Study Start: May 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: December 31, 2025
• Last Updated: May 11, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 2 years after the publication of the main results
• Access Criteria: No limit.

Locations

CN (1)