Dynamic Contrast Enhanced HCC SABR Liver Study

Carcinoma, Hepatocellular Clinical Trial

Official title:

Dynamic Contrast Enhanced Imaging of Patients Receiving SABR for Unresectable or Medically Inoperable Hepatocellular Carcinoma in BC

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02847767
• Other study ID #: H15-02341
• Status: Not yet recruiting
• Phase: N/A
• First received: July 5, 2016
• Last updated: July 25, 2016
• Start date: July 2016
• Est. completion date: October 2018

Study information

• Verified date: July 2016
• Source: British Columbia Cancer Agency
• Contact: Steven Thomas
• Phone: 604-877-6000
• Email: sthomas-02[@]bccancer.bc.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The high dose per fraction (>10Gy/fraction) used in Stereotactic Ablative Body Radiotherapy (SABR) has been shown to be more effective at local tumor control than treatments employing more conventional dose fractions. The mechanisms for this are currently under debate. One possible mechanism for this increased effectiveness is that high dose/fraction causes significant vascular damage to the tumor. This study hopes to measure vascular integrity pre and post SABR treatment using kinetic models obtained from dynamic contrast enhanced CT.

Description:

Purpose:

The purpose of this study is to determine if high dose per fraction SABR has an impact on the vasculature of both the tumor and of healthy liver tissue.

Hypothesis:

High dose / fraction in HCC patients with tumours < 5 cm will result in detectable changes to kinetic model parameters derived from dynamic contrast enhanced images.

Objectives:

Primary objective:

To quantify changes in tumor vascular support for patients receiving SABR.

Secondary objectives:

To investigate the correlation between PK derived model liver perfusion parameters and QoL metrics as measured by EORTC QLQ-C30 and FACT-Hep QoL assessments.

Research Methods:

Target population are patients receiving liver SABR for no more than 2 discrete liver tumors with a maximum dimension <5cm.

Perfusion CT Image Data Post Processing and Analysis. Patient motion will be corrected using deformable registration, fiducial tracking, and RPM breathing traces. Organ ROIs will be added to the perfusion image series by manually translating anatomical planning CT ROIs to the motion-corrected perfusion image series, or by algorithmically deforming planning ROIs. Portal vein and abdominal aorta ROIs will be demarcated.

Analysis will proceed via custom software we have built during related projects. Contrast enhancement time courses will be generated for key structures (i.e., abdominal aorta, portal vein, and gross liver tissues) and used to derive a variety of perfusion map images, such as liver perfusion, mean transit time, arterial fraction, and distribution volume. A distributed parameter model will be preferred for kinetic modeling. Supplementary non-parametric techniques will be used for other parameters of interest (e.g., IAUC, maximum slope).

Images acquired before and after treatment will be registered so that parameter maps can be compared on a per-patient basis. Changes in perfusion parameters will be characterized with special emphasis placed on regional structure and clustering effects. Pre and post parameter maps will be computed near individual-voxel level. Regions of interest (1) within or near tumour and (2) at a low-dose portion of liver will be defined. A distribution of parameters within each ROI will be used to generate estimates of the mean parameters and uncertainty. Estimates of mean parameters and whole distributions will be compared using standard statistical comparisons (t-test and Whitney respectively).

Quality of Life We will evaluate quality of life (QOL) in HCC patients treated with SBRT using EORTC QLQ-C30 and FACT-Hep QOL assessments at baseline, 3, 6, 9 and 12 months. Correlation between perfusion parameter changes and patient outcomes or QOL (second-order analysis) will be applied if statistically significant first-order parameter changes can be detected. Standard correlative measures such as the Pearson product-moment correlation measure will be used to assess statistical significance. As there is currently no data relating liver perfusion to toxicity or quality of life, this study will examine whether a change in liver perfusion is correlated with enhanced or reduced QOL.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All the following criteria must be met:

1. Age > 18 years old

2. Multi-phase CT scan and/or MRI of the liver within 8 weeks of radiation planning demonstrating:

• Liver tumours < 5 cm

• No more than 2 discrete liver tumours

• Normal liver > 700 cc

3. Patients must have HCC diagnosed by either: i) pathological confirmation, or ii) intrahepatic vascular enhancement of the lesion demonstrated by at least two imaging modalities, or iii) intrahepatic vascular enhancement of the lesion demonstrated by one imaging modality if AFP > 200 in the setting of liver cirrhosis or chronic hepatitis B without cirrhosis (EASL consensus guidelines [2])

4. Liver HCC must be deemed unresectable as determined by an experienced hepatobiliary surgeon, or the patient must be medically inoperable or refuse surgery,

5. Patients must be discussed in a multidisciplinary setting, with representatives from Medical Oncology, Radiation Oncology, Surgery, Interventional Radiology, and Hepatology. Patients must be considered ineligible for standard local treatments, including surgery, liver transplantation, radiofrequency ablation, and targeted biologics. Some subjects could be potential candidates for sorafenib but normally this treatment is not considered before all local treatment options have been considered, as the response rate to sorafenib is low (2% in the SHARP study). Patients might be candidates for sorafenib after progression on the study treatment or if they do not want to participate and in both cases they will be referred to a medical oncologist. Patients may have received prior TACE and had an incomplete response. Ineffective or incomplete TACE is defined as incomplete filling by lipiodol-doxorubicin mixture used by either angiography or CT =1 month after TACE or by increasing alpha-fetoprotein level. Patients must have recovered from the effects of previous therapies before SBRT with a minimum 4-week period between TACE and SBRT.

6. Eastern Clinical Oncology Group performance status 0, 1, or 2 (Appendix III), or a Karnofsky performance status of = 60 (Appendix IV)

7. Adequate organ function as assessed by the following blood work:

• Hemoglobin = 90 g/L

• Absolute neutrophil count = 1.0 bil/L

• Platelets = 50 bil/L

• AST and ALT not to exceed 3x upper limit of normal

8. Child-Turcotte-Pugh assessment within 8 weeks of treatment date (Appendix II):

• Bilirubin = 3 mg/dL (< 50 µmol/L)

• Albumin above 28 g/L

• INR < 1.7 and/or correctable with vitamin K (unless on anticoagulation therapy)

• No ascites or encephalopathy

• Child-Turcotte-Pugh score must be = 7

9. BCLC Stage B or C (portal venous invasion or liver hilum nodal disease only; (Appendix I)

10. Life expectancy > 6 months

11. No chemotherapy or systemic therapy concurrent with radiotherapy

12. Previous treatment(s) with radiofrequency ablation, surgery, TACE, Y90, percutaneous ethanol injection, or chemotherapy are not exclusion criteria provided that recurrence or lack of tumour response has been documented. Patients who decline, or not eligible for, these treatments will also be considered eligible.

13. Patient signs a study-specific informed consent form. If the patient's mental status precludes this, written informed consent may be given by the patient's legal representative. A translator will be provided if the patient has a language barrier.

14. Treatment plans meet acceptable dose constraints and Liver Veff is = 0.55

Exclusion Criteria:

1. Patients with active hepatitis, encephalopathy, or ascites related to liver failure

2. Female patients who are pregnant (verify with blood test if patient is pre-menopausal). Pre-menopausal patients may also not become pregnant during participation in this study.

3. Prior external beam radiation to the upper abdomen

4. Patients with distant metastases or extrahepatic nodal progression (patients with portal venous thrombosis and liver hilum nodal involvement remain eligible)

5. Patients who have < 700 cc of normal liver.

6. Child-Turcotte-Pugh scores > 7

7. BCLC Stage A, C (N1 and/or M1), D

8. Prior gastric, duodenal, or variceal bleed within the past 2 months

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Procedure:
• Perfusion Imaging
IV contrast perfusion CT will be performed at baseline and at 1 week after completing treatment. Perfusion imaging is similar to a diagnostic CT except a smaller region is serially imaged post contrast injection with multiple data acquisitions and high temporal resolution

Locations

Country	Name	City	State
Canada	BC Cancer Agency Fraser Valley Centre	Surrey	British Columbia
Canada	BC Cancer Agency Vancouver Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in tumour vasculature as assessed by changes PL derived model parameters	To quantify changes in tumor vascular support for patients receiving SABR.	1 week after cancer treatment	No
Secondary	Association (correlation) between aggregate QOL scores and PK derived model parameters	To investigate the correlation between PK derived model liver perfusion parameters and QOL metrics as measured by EORTC QLQ-C30 and FACT-Hep QOL assessments.	1 week after cancer treatment	No