| CTRI Number |
CTRI/2024/02/062782 [Registered on: 19/02/2024] Trial Registered Prospectively |
| Last Modified On: |
28/02/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Observational |
|
Type of Study
|
Cohort Study |
| Study Design |
Other |
|
Public Title of Study
|
Efficacy and Safety of SBRT Combined With Atezolizumab Plus Bevacizumab (drug) vs Atezolizumab Plus Bevacizumab (drug) in Treating Unresectable Advance Hepatocellular Carcinoma (Liver cancer). |
|
Scientific Title of Study
|
Efficacy and Safety of SBRT Combined With Atezolizumab Plus Bevacizumab vs Atezolizumab Plus Bevacizumab in Treating Unresectable Advance Hepatocellular Carcinoma (SAB - A Prospective Observational Study). |
| Trial Acronym |
SAB |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| None |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Phool Chand |
| Designation |
Senior Resident,Department of hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3360, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI
110070
India |
| Phone |
01146300000 |
| Fax |
|
| Email |
phoolchand99@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Vinod Arora |
| Designation |
Associate Professor, Department of Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3360, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI
110070
India |
| Phone |
01146300000 |
| Fax |
|
| Email |
VINOD_UCMS@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Vinod Arora |
| Designation |
Associate Professor, Department of Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3360, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
DELHI
110070
India |
| Phone |
01146300000 |
| Fax |
|
| Email |
VINOD_UCMS@yahoo.com |
|
|
Source of Monetary or Material Support
|
| Institute of Liver & Biliary Sciences,D-1,Vasant Kunj,New Delhi-110070 |
|
|
Primary Sponsor
|
| Name |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3360, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
|
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Phool Chand |
Institute of Liver and Biliary Sciences |
Room No. 3360, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI |
01146300000
phoolchand99@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, Institute of Liver and Biliary Sciences |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K769||Liver disease, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
NIL |
NIL |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
1. Age 18–70 years.
2. Unresectable advance HCC with PVT
3. At least one measurable (measurable according to Response Evaluation Criteria In Solid Tumors (mRECIST untreated lesions.
4. Patients with hepatitis B virus (HBV) infection: HBV-DNA less than 500 IU per mL obtained within 28 days before the start of study treatment and received anti-HBV treatment for at least 28 days before entering the study.
5. Patients with hepatitis C virus (HCV) infection: HCV-DNA less than 500 IU per mL obtained within 28 days before the start of study treatment and received anti-HCV treatment for at least 28 days before entering the study.
6. Maximum diameter of tumor less than equals to 15cm
7. Maximum number of tumor nodules less than equals to 5
8. Liver function: Child-Pugh class A, B7; normal liver volume is more than 800cm3.
9. Karnofsky performance status more than equals to 80%
10. The expected survival of the patient is more than 6 months.
11. Agree to accept post-procedure follow-up required by the design of this study.
12. The following conditions are met:
i. Platelet more than equals to 60 per L; White blood cell more than equals to 3.0×109 per L; Hemoglobin more than equals to 85 g per L; Serum creatinine less than equals to 1.4 upper limit;. PT-INR less than equals to 1.7
|
|
| ExclusionCriteria |
| Details |
1. Patients with untreated or incompletely treated esophageal and or gastric varices with associated bleeding or at high risk of bleeding.
2. Coinfection with HBV and hepatitis C virus (HCV).
3. Symptomatic, untreated or progressively progressive central nervous system (CNS) metastases.
4. The patient cannot receive follow-up or is participating in other clinical trials.
5. Subjects deemed unsuitable for inclusion in this study by the investigator.
6. Current or past autoimmune disease or immunodeficiency.
7. History of leptomeningitis.
8. Idiopathic pulmonary fibrosis, organising pneumonia or evidence of active pneumonia on chest.
9. Known active tuberculosis.
10. Severe infection within 4 weeks prior to initiation of study treatment
11. A potential subject who meets any of the following criteria will be excluded from participation in this study:
i) Previous radiotherapy to the liver
ii) Known current pregnancy
iii) Loss of fat planes of tumor with organ at risk like the esophagus, stomach, duodenum, small bowel on CT or on MRI
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Objective response rate (ORR), which is defined as the proportion of patients with complete response (CR) and partial response (PR) at 6 months . CR or PR is assessed in accordance with mRECIST. |
6 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Overall survival at 3, 6 and 12 months |
3, 6 and 12 months |
| Disease control rate (DCR) at 3, 6 and 12 months, defined as the percentage of subjects with the best response as CR, PR or stable disease (SD) |
3, 6 and 12 months |
| Progression-free survival (PFS) at 3, 6 and 12 months |
3, 6 and 12 months |
| Adverse events 3, 6 and 12 months |
3, 6 and 12 months |
| Biomarkers change( AFP , PIVKA II) at 3, 6 and 12 months |
3, 6 and 12 months |
|
|
Target Sample Size
|
Total Sample Size="40"
Sample Size from India="40"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
26/02/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
SBRT,
atezolizumab, and bevacizumab have different mechanisms of action and can
potentially have synergistic effects when combined. SBRT delivers targeted
radiation to the tumor, while atezolizumab enhances the immune response, and
bevacizumab inhibits angiogenesis. The combination of SBRT with atezolizumab
and bevacizumab will result in improved tumor response rates as compared to
atezolizumab and bevacizumab alone in patients with advance unresectable
hepatocellular carcinoma (HCC). Up until now, no study has been done that has
compared SBRT with atezolizumab, and bevacizumab in unresectable advance
hepatocellular carcinoma. In this study the patients will receive these above-mentioned
treatments as a part of their treatment protocol. These treatments are not
given under this study. However in our observational study, we aim to compare
the efficacy and safety of SBRT combined with atezolizumab and bevacizumab
versus atezolizumab and bevacizumab alone in the treatment of unresectable
advance hepatocellular carcinoma (HCC).
Hypothesis:
The combination of SBRT with atezolizumab and bevacizumab will result in
improved tumor response rates as compared to atezolizumab and bevacizumab alone
in patients with advance unresectable hepatocellular carcinoma (HCC).
AIM:- The aim of this study is to compare the
efficacy and safety of SBRT combined with atezolizumab and bevacizumab versus
atezolizumab and bevacizumab alone in the treatment of unresectable advance
hepatocellular carcinoma (HCC).
Study design:
• A prospective observational study.
• Single Centre.
• Open label.
• The study will be conducted in
Department of Hepatology, ILBS.
Study
period: 1 years after ethical approval.
Sample size:
• Assuming that objective response
rate with immunotherapy is 30%, further adding SBRT along with immunotherapy is
increased by 50% that is objective response rate by adding SBRT is 80% .
• With âº-5 and power
80% we need to enroll 36 cases and further adding 10% dropout rate we need to
enroll 40 cases i.e. 20 in each group.
Monitoring and
assessment: All the parameters of the objective and also noted any adverse
effects.
STATISTICAL
ANALYSIS:
The continuous
data will be represented as mean +/- SD or median (IQR). The categorical data
will be represented as median (IQR).The comparison of continuous data will be
done by using either Student’s t test or Mann -Whitney test as appropriate. The
Kaplan Meier and Cox regression will be used for survival analysis. Besides
this an appropriate analysis will be done at the time of data analysis. P value
< 0.05 will be considered as significant. |