| CTRI Number |
CTRI/2017/09/009879 [Registered on: 21/09/2017] Trial Registered Prospectively |
| Last Modified On: |
21/09/2017 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Radiation Therapy |
| Study Design |
Other |
|
Public Title of Study
|
A study to determine the efficacy of radiation therapy and specialized drug treatment in the management of liver cancer |
|
Scientific Title of Study
|
“Randomized study of stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) in hepatocelluar carcinoma |
| Trial Acronym |
SBRT IAEA Study |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 1750 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Supriya Sastri nee Chopra |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No:-1120, 11th Floor, Homi Bhabha Building, Tata Memorial Hospital, Parel, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
|
| Fax |
|
| Email |
supriyasastri@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Supriya Sastri nee Chopra |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No:-1120, 11th Floor, Homi Bhabha Building, Tata Memorial Hospital, Parel, Mumbai
MAHARASHTRA
400012
India |
| Phone |
|
| Fax |
|
| Email |
supriyasastri@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Supriya Sastri nee Chopra |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No:-1120, 11th Floor, Homi Bhabha Building, Tata Memorial Hospital, Parel, Mumbai
MAHARASHTRA
400012
India |
| Phone |
|
| Fax |
|
| Email |
supriyasastri@gmail.com |
|
|
Source of Monetary or Material Support
|
| IAEA Technical Officer: Mr Rajiv Prasad
Radiation Oncologist
International Atomic Energy Agency, Vienna International Centre, P.O. Box 100, 1400 Vienna, Austria |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
IAEA Technical Officer: Mr Rajiv Prasad
Radiation Oncologist
International Atomic Energy Agency, Vienna International Centre, P.O. Box 100, 1400 Vienna, Austria
|
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India
Denmark
Egypt
Malaysia |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Supriya Sastri |
Tata Memorial Centre |
3rd floor room no 322 Homibhaba building Department of Radiation oncology Dr. Ernest Borges Marg, Parel, Mumbai
Mumbai
MAHARASHTRA |
9930958309
supriyasastri@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Hepatocellular cancer, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Stereotactic Body Radiation Therapy |
The following techniques contributing to the high precision are used in SBRT: Stereotactic body frame (SBF) with abdominal compression, multimodality imaging for treatment planning, daily imaging in the treatment position (in or outside the treatment room), EPID-imaging or cone-beam CT scan (CBCT) in the treatment room, use of a multi-slice CT scanner (4DCT) instead of a single slice scanner to avoid imaging artifacts, use of implanted gold markers, active breathing control (ABC), and tumor tracking (robotic Cyberknife). Immbolization is done and treatment planning by imaging and radiation dose 3-fraction schedule should be preferred over a 6-fraction schedule. |
| Comparator Agent |
Transarterial chemoembolization |
transarterial chemoembolization
DEB-TACE procedureTranscatheter treatment of hepatocellular carcinoma with Doxorubicin loaded DC/LC beads. Microcatheter, superselective cauterization, C-arm 2-D X-ray imaging combined with CBCT scan following the procedure is recommended.
Response by m-RECIST 4 weeks after treatment, every TACE.
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
•HCC (biopsy or radiological diagnostic (>1 cm, enhancing in arterial phase and wash-out in later phases).
•Number of lesions: not more than 3 lesions
•Lesion size: up to 10 cm for a single lesion (and up to 10 cm cumulative diameter, if there is more than 1 lesion)
•Child-Pugh A or B (<7) on examination within 6 weeks prior to study entry
•BCLC Stage A/B
•Must be fit (eligible) for SBRT and TACE
• Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) or if these options are not available
•Distance between GTV (lesion) and luminal structures (including esophagus, stomach, duodenum, small or large bowel) is >10 mm
•All blood work obtained within 2 weeks prior to study entry with adequate organ function defined as follows:
oAbsolute neutrophil count (ANC) ≥ 1,500 cells/mm3
oPlatelets ≥50,000 cells/mm3
oHemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
oTotal bilirubin < 2 mg/dL
oProthrombin time/INR < 1.4 (unless on Coumadin/Warfarin)
oAlbumin ≥ 28 g/L
oAST (and ALT) < 5 times ULN
oSerum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min
oMay have had previous surgery, ethanol injection and RFA to the liver
|
|
| ExclusionCriteria |
| Details |
•Not suitable for clinical trial or follow-up
•Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (Note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
. No active cancer therapy.
•Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) Raoul et al (2011)
oNon-enhancing HCC on CT or CT-angio or
oPortal vein thrombosis/macroscopic venous invasion
•Arterio-portal and arterio-venous fistulas observed on pre-study imaging (if it is found during the TACE, the fistula may be embolized before injection of the drug).
•Evidence of metastatic disease including nodal or distant metastases.
•Previous TACE or radiation to the liver (including SIRT)
•Life-threatening condition (including untreated HIV and active hepatitis B/C)
oDetectable HBeAg and HBV viral load > 20,000 IU/mL or
oHBeAg-negative chronic hepatitis B and HBV viral load >2,000 IU/mL
oIf HBV-DNA copy is higher than 500 copies/ml, anti-viral therapy, such as Entecavir followed by observation for 2 weeks.
oIf anti-HCV antibody is positive (may be false positive) and increased HCV viral load indicating active disease. Active HCV should be treated sufficiently before inclusion in the study. Below 2 million copies per milliliter (mL) is related to chronic hepatitis C that does not need antiviral therapy.
oPatients with active hepatitis B or C should be on treatment for at least 4 weeks before inclusion in the trial
•On sorafenib or other antineplastic drug therapy within 7 days before inclusion (not accepted until time of progression).
•Pregnancy or women of childbearing potential require a negative pregnancy test within 28 days
|
|
|
Method of Generating Random Sequence
|
Other |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Progression at 1 year: local, intra- and extrahepatic progression |
1 year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
•Response rate
•Local failure –
•Intrahepatic failure – more than 1 cm from the original tumor volume
•Extrahepatic failure
•Overall survival
•Toxicity – consecutive follow-up.
•QoL (EORTC QLQC30, EORTC QLQ-HCC18)
•Cost-benefit treatment, costs of complication (hospitalization) and patient care/additional therapy for HCC following protocol therapy).
|
3 year |
|
|
Target Sample Size
|
Total Sample Size="180"
Sample Size from India="30"
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)
|
01/10/2017 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
01/10/2017 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
HCC a major health problem worldwide, more so in developing countries especially in Asia and Africa and has a dismal prognosis particularly in advance stages. SBRT an emerging radiation treatment modality offers a potential therapy for sustained local control or potentially valuable salvage therapy for many tumour types including all stages of HCC. For unresectable cases of HCC, both TACE and SBRT have been used but there has not been any randomized trial to compare between these two modalities. Therefore, a clinical study comparing SBRT and TACE will be very significant as it addresses a common problem especially in Asia and Africa. So If positive then the results will redefine standards of care for HCC. As of now we cannot describe any direct benefits to patient or society. Objectives of the project: To demonstrate non-inferiority of SBRT compared to TACE in terms of any disease progression in patients with HCC, who have not previously received SBRT or TACE. Expected outcomes:This is a non-inferiority study with the objective to demonstrate non-inferiority of SBRT to TACE in terms of any disease progression in patients with HCC, who have not previously received SBRT or TACE. On the basis of phase II data the present study tests if use of SBRT is associated with improved progression free survival in patients with hepatocellular cancer. If positive then the results will provide another alternative standard of care for HCCSBRT if redefined as an alternative standard can be completed in 2weeks whereas 3-4 TACE procedures take upto 4-5 months of treatment and are associated with significant procedureal costs. Additionally multiple visits and investigations prior to procedure add on to the treatment delivery costs. If SBRT is found to be non inferior it will also provide a more cost effective alternative for treatment of patients with unresectable HCC. |