Back to results68Ga-NY104 PET/CT in Von Hippel-Lindau Disease
Primary Purpose
Von Hippel-Lindau Disease
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis) 68Ga-NODAGA-LM3 PET/CT (exploratory)
Sponsored by
About this trial
This is an interventional diagnostic trial for Von Hippel-Lindau Disease
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Sites / Locations
- Peking Union Medical College HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Diagnostic imaging arm
Arm Description
68Ga-NY104 PET/CT Contrast-enhanced MRI of the brain and contrast-enhanced CT of abdomen and pelvis 68Ga-NODAGA-LM3 PET/CT (exploratory)
Outcomes
Primary Outcome Measures
Binary reading of lesions identified on 68Ga-NY104 PET/CT
Define lesion as PET positive or PET negative lsion
The number of (68Ga-NY104) PET positive lesions
Count the number of lesions (if more than 10, record it as >10)
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
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
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.
The number of conventional imaging positive lesions
Count the number of lesions (if more than 10, record it as >10)
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
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
Secondary Outcome Measures
The intent of initial management plan (Plan 1) based on conventional imaging
Management plan intent (curative, palliative or surveillance): it should be noted that the curative intent in the present study could be organ specific. For example, if the patient has non-symptomatic CNS hemangioblastomas and a solitary renal cell carcinoma, the intent to resect the renal cell carcinoma should be defined as "curative" even if the CNS hemangioblastomas are left undealt with.
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.
Management plan intent (curative, palliative or surveillance): it should be noted that the curative intent in the present study could be organ specific. For example, if the patient has non-symptomatic CNS hemangioblastomas and a solitary renal cell carcinoma, the intent to resect the renal cell carcinoma should be defined as "curative" even if the CNS hemangioblastomas are left undealt with.
The specified management plan of initial management plan (Plan 1) based on conventional imaging
Specified management plan for each patient including details of surgery or medical treatment or active surveillance. For surgery, this will include type of surgery (e.g., partial nephrectomy or radical nephrectomy, with / without lymph node dissection). For medical treatment, this will include the regimen, dose, and frequency of the treatment plan. For active surveillance, this will include the type and frequency of modality.
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.
Specified management plan for each patient including details of surgery or medical treatment or active surveillance. For surgery, this will include type of surgery (e.g., partial nephrectomy or radical nephrectomy, with / without lymph node dissection). For medical treatment, this will include the regimen, dose, and frequency of the treatment plan. For active surveillance, this will include the type and frequency of modality.
Full Information
NCT ID
NCT05810246
First Posted
March 9, 2023
Last Updated
May 9, 2023
Sponsor
Peking Union Medical College Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05810246
Brief Title
68Ga-NY104 PET/CT in Von Hippel-Lindau Disease
Official Title
68Ga-NY104 PET/CT and Conventional Imaging in Patients With Von Hippel-Lindau Disease: a Prospective, Single-center, Single-arm, Comparative Imaging Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Anticipated)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
To determine the incremental management impact of 68Ga-NY104 PET/CT
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
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.)
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Von Hippel-Lindau Disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Diagnostic imaging arm
Arm Type
Experimental
Arm Description
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
Intervention Name(s)
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 Description
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.
Primary Outcome Measure Information:
Title
Binary reading of lesions identified on 68Ga-NY104 PET/CT
Description
Define lesion as PET positive or PET negative lsion
Time Frame
From study completion to 1 month after completion
Title
The number of (68Ga-NY104) PET positive lesions
Description
Count the number of lesions (if more than 10, record it as >10)
Time Frame
From study completion to 1 month after completion
Title
The number of (68Ga-NY104) PET positive regions
Description
Any region with at least one (68Ga-NY104) PET positive lesion is considered (68Ga-NY104) PET positive VHL-related region
Time Frame
From study completion to 1 month after completion
Title
The number of (68Ga-NY104) PET positive patients
Description
Any patient with at least one (68Ga-NY104) PET positive lesion is considered (68Ga-NY104) PET positive VHL-related patient
Time Frame
From study completion to 1 month after completion
Title
Scoring of lesions identified on conventional imaging as very unlikely / unlikely / indeterminate / likely / very likely (score 1-5)
Description
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.
Time Frame
From study completion to 1 month after completion
Title
The number of conventional imaging positive lesions
Description
Count the number of lesions (if more than 10, record it as >10)
Time Frame
From study completion to 1 month after completion
Title
The number of conventional imaging positive regions
Description
Any region with at least one conventional-imaging positive VHL-related lesion is considered conventional-imaging positive VHL-related region
Time Frame
From study completion to 1 month after completion
Title
The number of conventional imaging positive patients
Description
Any patient with at least one conventional-imaging positive VHL-related lesion is considered conventional-imaging positive VHL-related patient
Time Frame
From study completion to 1 month after completion
Secondary Outcome Measure Information:
Title
The intent of initial management plan (Plan 1) based on conventional imaging
Description
Management plan intent (curative, palliative or surveillance): it should be noted that the curative intent in the present study could be organ specific. For example, if the patient has non-symptomatic CNS hemangioblastomas and a solitary renal cell carcinoma, the intent to resect the renal cell carcinoma should be defined as "curative" even if the CNS hemangioblastomas are left undealt with.
Time Frame
From study completion to 1 month after completion
Title
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.
Description
Management plan intent (curative, palliative or surveillance): it should be noted that the curative intent in the present study could be organ specific. For example, if the patient has non-symptomatic CNS hemangioblastomas and a solitary renal cell carcinoma, the intent to resect the renal cell carcinoma should be defined as "curative" even if the CNS hemangioblastomas are left undealt with.
Time Frame
From study completion to 1 month after completion
Title
The specified management plan of initial management plan (Plan 1) based on conventional imaging
Description
Specified management plan for each patient including details of surgery or medical treatment or active surveillance. For surgery, this will include type of surgery (e.g., partial nephrectomy or radical nephrectomy, with / without lymph node dissection). For medical treatment, this will include the regimen, dose, and frequency of the treatment plan. For active surveillance, this will include the type and frequency of modality.
Time Frame
From study completion to 1 month after completion
Title
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.
Description
Specified management plan for each patient including details of surgery or medical treatment or active surveillance. For surgery, this will include type of surgery (e.g., partial nephrectomy or radical nephrectomy, with / without lymph node dissection). For medical treatment, this will include the regimen, dose, and frequency of the treatment plan. For active surveillance, this will include the type and frequency of modality.
Time Frame
From study completion to 1 month after completion
Other Pre-specified Outcome Measures:
Title
Binary reading of lesions identified on 68Ga-NODAGA-LM3 PET/CT as PET positive lesions or PET negative lesions
Description
Define lesion as PET positive or PET negative lsion
Time Frame
From study completion to 1 month after completion
Title
The number of (68Ga-NODAGA-LM3) PET positive lesions
Description
Count the number of lesions (if more than 10, record it as >10)
Time Frame
From study completion to 1 month after completion
Title
The number of (68Ga-NODAGA-LM3) PET positive regions
Description
Any region with at least one (68Ga-NODAGA-LM3) PET positive lesion is considered (68Ga-NODAGA-LM3) PET positive VHL-related region
Time Frame
From study completion to 1 month after completion
Title
The number of (68Ga-NODAGA-LM3) PET positive patients
Description
Any patient with at least one (68Ga-NODAGA-LM3) PET positive lesion is considered (68Ga-NODAGA-LM3) PET positive VHL-related patient
Time Frame
From study completion to 1 month after completion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Li Huo, MD
Phone
18612672038
Email
huoli@pumch.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Wenjia Zhu, MD
Phone
18614080164
Email
zhuwenjia_pumc@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Huo, MD
Organizational Affiliation
Peking Uion Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenjia Zhu, MD
Email
zhuwenjia_pumc@163.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Available upon request
IPD Sharing Time Frame
Within 2 years after the publication of the main results
IPD Sharing Access Criteria
No limit.
Learn more about this trial
68Ga-NY104 PET/CT in Von Hippel-Lindau Disease
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