## Protocol Section
### Identification Module
**NCT ID:** NCT06391879

**Brief Title:** Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma

**Official Title:** Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma Based on Accurate Genotyping: a Population-based Study

#### Organization Study ID Info
**ID:** 2023#395-002
#### Organization
**Class:** OTHER
**Full Name:** Peking University First Hospital
### Status Module
#### Completion Date
**Date:** 2025-08-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-29

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-06-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-09-08

**Type:** ACTUAL

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-04-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-25
**Study First Submit QC Date:** 2024-04-29
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Peking University First Hospital

#### Responsible Party

**Investigator Affiliation:** Peking University First Hospital

**Investigator Full Name:** GONG Kan

**Investigator Title:** Chief physician

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** VHL syndrome is a rare hereditary tumor syndrome caused by mutation of tumor suppressor gene VHL. One of the most important clinical manifestations and main cause of death is VHL-related renal cell carcinoma (RCC). Facing the challenges of multilesion of both kidneys, slow progress and life-long repeated surgeries in VHL-related RCC, individualized prediction of the best surgical treatment time and reduction of times of surgeries are very important to improve the prognosis of patients with VHL syndrome. Therefore, there is an urgent need to establish a more effective and accurate prediction model for the natural course of VHL syndrome. This cohort-study aims to retrospectively and prospectively analyze the factors related to the natural course of VHL-related RCC. At the same time, some patients were selected for prospectively continuous molecular evolution dynamic monitoring after comprehensively considering the results of single cell sequencing, whole genome and metabonomic sequencing. This study will provide scientific basis for accurate diagnosis and treatment of natural course of VHL-related RCC.

**Detailed Description:** VHL syndrome is a rare hereditary tumor syndrome caused by mutation of tumor suppressor gene VHL. One of the most important clinical manifestations and main cause of death is VHL-related renal cell carcinoma (RCC). Previous small sample studies have confirmed that the natural course of VHL-related RCC is different from that of sporadic RCC. Facing the challenges of multilesion of both kidneys, slow progress and life-long repeated surgeries in VHL-related RCC, individualized prediction of the best surgical treatment time and reduction of times of surgeries are very important to improve the prognosis of patients with VHL-related RCC. Therefore, there is an urgent need to establish a more effective and accurate prediction model for the natural course of VHL syndrome. Based on the previous establishment of the largest biobank of VHL syndrome in Asia, as well as the unique characteristics and genotype-phenotypic relationship of patients in Chinese population, this cohort-study aims to retrospectively and prospectively analyze the factors related to the natural course of VHL-related RCC. At the same time, some patients were selected for prospectively continuous molecular evolution dynamic monitoring after comprehensively considering the results of single cell sequencing, whole genome and metabonomic sequencing. This study will systematically analyze the specific molecular characteristic and evolution of VHL-related different from sporadic RCC, reveal new specific driving genes and their molecular regulatory mechanisms, and establish a multi-dimensional prediction model of natural course of VHL-related RCC based on accurate genotyping. It will provide scientific basis for accurate diagnosis and treatment of natural course of VHL-related RCC.

### Conditions Module

**Conditions:**

- VHL Syndrome

- Renal Cell Carcinoma

**Keywords:**

- VHL

- VHL syndrome

- Renal cell carcinoma

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 300

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** This cohort incorporates subjects with VHL-related renal cell carcinoma.

**Intervention Names:**

- Genetic: Single cell sequencing, whole genome and metabolomic sequencing

**Label:** VHL-related RCC cohort

### Interventions

#### Intervention 1

**Arm Group Labels:**

- VHL-related RCC cohort

**Description:** The blood specimen of subjects in this cohort would be collected to conduct single cell sequencing, whole genome and metabolomic sequencing.

**Name:** Single cell sequencing, whole genome and metabolomic sequencing

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** The tumor size was measured annually and the tumor growth rate was calculated.

**Measure:** Tumor growth rate

**Time Frame:** From date of diagnosis of the VHL-related RCC until the date of surgical treatment, death from any cause or the date of last follow-up, whichever came first, assessed up to 60 years.

#### Secondary Outcomes

**Description:** OS was calculated as the time interval from the diagnosis of the VHL-related RCC to death or the time to the last follow-up.

**Measure:** Overall survival (OS)

**Time Frame:** From date of diagnosis of the VHL-related RCC until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 20 years.

**Description:** CSS was calculated as the time interval from the diagnosis of the VHL-related RCC to death from the same disease or the last follow-up.

**Measure:** Cancer-specific survival (CSS)

**Time Frame:** From date of diagnosis of the VHL-related RCC until the date of death from the same disease or the date of last follow-up, whichever came first, assessed up to 20 years.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Diagnosis of VHL syndrome based on clinical diagnostic criteria or genetic test results of syndrome
* Upon enrollment, multiple organ assessments for VHL syndrome should be completed, including fundus examination, CT/MR examination of the brain, spinal cord, and abdominal and pelvic organs.
* If subjects have undergone surgery for renal tumors, the follow-up observation time in each branch center before surgery should be more than 12 months, and imaging examinations should be performed at least once every 6 months.

Exclusion Criteria:

* Do not meet the clinical diagnostic criteria for VHL disease or the genetic test is negative
* Other hereditary RCC syndromes

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Based on the previous establishment of the largest biobank of VHL syndrome in Asia, as well as the unique characteristics and genotype-phenotypic relationship of patients in Chinese population, this cohort-study aims to retrospectively and prospectively incorporated patients with VHL-related RCC.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** kan.gong@bjmu.edu.cn

**Name:** Kan Gong

**Phone:** (86)-010-83572075

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** bdyyll@126.com

- **Name:** Yanyan Yu

- **Phone:** +86 1066119025

- **Role:** CONTACT

**Country:** China

**Facility:** Peking University First Hospital

**State:** Beijing

**Status:** RECRUITING

**Zip:** 100034

#### Overall Officials

**Official 1:**

**Affiliation:** Peking University First Hospital

**Name:** Kan Gong

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000007680

- Term: Kidney Neoplasms

- ID: D000014571

- Term: Urologic Neoplasms

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000007674

- Term: Kidney Diseases

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000020752

- Term: Neurocutaneous Syndromes

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000000798

- Term: Angiomatosis

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000072661

- Term: Ciliopathies

- ID: D000000015

- Term: Abnormalities, Multiple

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M5548

- Name: Carcinoma, Renal Cell

- Relevance: HIGH

- As Found: Renal Cell Carcinoma

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M9699

- Name: Von Hippel-Lindau Disease

- Relevance: HIGH

- As Found: VHL Syndrome

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M10703

- Name: Kidney Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17320

- Name: Urologic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M10698

- Name: Kidney Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22509

- Name: Neurocutaneous Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M4126

- Name: Angiomatosis

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M1076

- Name: Ciliopathies

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M14

- Name: Abnormalities, Multiple

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T4906

- Name: Renal Cell Carcinoma

- Relevance: HIGH

- As Found: Renal Cell Carcinoma

- ID: T1341

- Name: Clear Cell Renal Cell Carcinoma

- Relevance: HIGH

- As Found: Renal Cell Carcinoma

- ID: T5876

- Name: Von Hippel-Lindau Disease

- Relevance: HIGH

- As Found: VHL Syndrome

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000002292

- Term: Carcinoma, Renal Cell

- ID: D000006623

- Term: Von Hippel-Lindau Disease

### Misc Info Module

- Version Holder: 2024-05-24
