## Protocol Section
### Identification Module
**NCT ID:** NCT06434480

**Brief Title:** SBRT in HCC With Oligoprogression on Atezo-Bev

**Official Title:** Stereotactic Body Radiotherapy (SBRT) in Advanced Hepatocellular Carcinoma With Oligoprogression on Atezolizumab Plus Bevacizumab

#### Organization Study ID Info
**ID:** HCC07X
#### Organization
**Class:** OTHER
**Full Name:** Chinese University of Hong Kong
### Status Module
#### Completion Date
**Date:** 2028-03-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-28

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-03-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-02

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-28
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Chinese University of Hong Kong

#### Responsible Party

**Investigator Affiliation:** Chinese University of Hong Kong

**Investigator Full Name:** Landon Chan

**Investigator Title:** Assistant Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** HCC is a huge healthcare burden in Hong Kong and is one of the top 5 cancers in terms of incidence and mortality in Hong Kong. Patients with advanced HCC are treated with immunotherapy-based combination atezolizumab plus bevacizumab as first-line treatment as a standard of care. At the moment, there is limited evidence to guide subsequent treatments after patients progressed on atezolizumab plus bevacizumab. Oligoprogression is a term used to describe patients who had limited progression (usually less than 3 sites) on systemic therapy, with the rest of the lesions controlled. Previous studies in non-HCCs have shown that addition of locoregional treatment (e.g. radiotherapy) may prolong the use of systemic therapy, resulting in improved survival, but this has been relatively unexplored for HCC. In this prospective, single-arm study, we aim to evaluate the treatment outcome, efficacy and safety of the addition of radiotherapy to oligoprogressive sites for patients who had limited progression on atezolizumab plus bevacizumab.

### Conditions Module

**Conditions:**

- HCC

**Keywords:**

- SBRT in HCC

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** After screening procedures, suitable patients are consented and enrolled with the following treatment being given

* Continue Atezolizumab 1200mg Day 1 plus Bevacizumab 15mg/kg Day 1, given intravenously every 3 weeks, till the next progression, or death.
* Radiotherapy will start 4 to 6 weeks after consent
* For intrahepatic progression: 27.5-50Gy in 5 fractions over 2 weeks will be given.
* For extrahepatic progression: an aim to give ablative dose (i.e. BED10≥100Gy) will be given (allow lower dose based on nearby OAR dose constraints and is at the discretion of the treating radiation oncologist)
* Bevacizumab will need to be withhold 4 weeks prior and after radiotherapy.
* Dose constraints to organ at risk (OAR) will take reference from RTOG-1112 and UK 2022 consensus on normal tissue dose-volume constraints

**Intervention Names:**

- Radiation: Stereotactic Body Radiation Therapy (SBRT)

**Label:** Radiotherapy

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Radiotherapy

**Description:** * For intrahepatic progression: 27.5-50Gy in 5 fractions over 2 weeks will be given.
* For extrahepatic progression: an aim to give ablative dose will be given.

**Name:** Stereotactic Body Radiation Therapy (SBRT)

**Type:** RADIATION

### Outcomes Module

#### Primary Outcomes

**Measure:** Progression-free survival (PFS) with the addition of SBRT to oligo-progressive sites

**Time Frame:** 2 years

#### Secondary Outcomes

**Measure:** Overall survival (OS)

**Time Frame:** 2 years

**Measure:** Objective response rates (ORR) of the irradiated lesion(s)

**Time Frame:** 2 years

**Measure:** Overall objective response rates (ORR)

**Time Frame:** 2 years

**Measure:** Additional treatment related adverse events (TRAE)

**Time Frame:** 2 years

**Description:** Four types of progression pattern:

* EHG (extrahepatic growth)
* IHG (intrahepatic growth)
* NEH (new extrahepatic lesion)
* NIH (new intrahepatic growth)

**Measure:** Pattern of progression

**Time Frame:** 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Patients aged ≥ 18 years old
2. ECOG performance 0 to 1
3. Confirmed diagnosis of HCC
4. Oligoprogression on Atezolizumab plus Bevacizumab, as defined as ≤3 lesions (intra- and extrahepatic lesions all together; vascular tumor thrombus is counted as one lesion)
5. Progressed lesion(s) amenable to SBRT:

   * At most one site of intrahepatic and one site of extrahepatic lesion will be irradiated
   * For intrahepatic progression:

     * Number of intrahepatic progression ≤ 3
     * Total intrahepatic tumours ≤ 5
     * Maximum sum of HCC ≤ 20cm
     * Any one HCC ≤ 15cm
     * Normal liver volume minus intrahepatic GTV \> 700cc
     * Mean liver dose ≤ 15Gy
     * No measurable common or main branch biliary duct involvement
     * No direct tumor invasion into the stomach, duodenum, small bowel or large bowel
   * For extrahepatic progression:

     * Maximal tumor size ≤ 3cm
     * Respective dose constraints of organ at risks as listed on the UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy can be met.
6. Prior radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) are eligible
7. Child-Pugh A liver function
8. Life expectancy longer than 12 weeks
9. At least one measurable treatment lesion according to RECIST 1.1
10. Written informed consent must be obtained prior to any study related procedures
11. Adequate haematological function (Hb ≥ 8.5g/dL; Plt ≥ 75x109/L; ANC ≥ 1.5x109/L; INR ≤ 1.5)
12. Adequate hepatic function (albumin ≥ 28g/l; Bilirubin ≤ 1.5xULN; ALT \< 5 times upper limit normal)
13. Adequate renal function (serum creatinine ≤ 1.5 times the upper limit of normal range; Na ≥ 130mmol/L; K ≥ 3.0mmol/L)
14. Able to read, understand and provide written consent

Exclusion Criteria:

1. History of another malignancy except appropriately-treated BCC of skin or CIN of cervix during the last 5 years
2. Previous radiotherapy to the abdomen
3. Previous yttrium-90 chemoembolization
4. Repetitive history of non-healing wounds or ulcers within 2 months of inclusion
5. Pregnant or lactating females at any time during the study
6. Active autoimmune disease requiring systemic therapy in the past 2 years
7. Diagnosis of immunodeficiency (including HIV)
8. Ongoing corticosteroid therapy \>10mg prednisone daily

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** landon.chan@cuhk.edu.hk

**Name:** Landon L CHAN, MBChB, MSc

**Phone:** 3505 1042

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Hong Kong

**Contacts:**

***Contact 1:***

- **Email:** landon.chan@cuhk.edu.hk

- **Name:** Landon L CHAN, MBChB, MSc

- **Phone:** 3505 1042

- **Role:** CONTACT

**Country:** Hong Kong

**Facility:** Department of Clinical Oncology, Prince of Wales Hospital

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M9613

- Name: Carcinoma, Hepatocellular

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M246

- Name: Bevacizumab

- Relevance: LOW

- As Found: Unknown

- ID: M349417

- Name: Atezolizumab

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
