Combined Radiotherapy and Sorafenib in Patients With Hepatoma

Hepatocellular Carcinoma Clinical Trial

Official title:

Combined Radiotherapy and Sorafenib in Patients With Hepatoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01319942
• Other study ID #: RT-sorafenib
• Status: Recruiting
• Phase: N/A
• First received: July 20, 2010
• Last updated: March 21, 2011
• Start date: June 2010
• Est. completion date: June 2013

Study information

• Verified date: March 2011
• Source: China Medical University Hospital
• Contact: Shang-Wen Chen, MD
• Phone: 886-4-22052121
• Email: vincent1680616[@]yahoo.com.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

This study aims to test the efficacy of combined radiotherapy and sorafenib in patients with locally advanced hepatocellular carcinoma.

Description:

Hepatocellular carcinoma (HCC) is a common cause of cancer mortality in Asia. Most patients present with intermediate or advanced disease. Percutaneous ethanol injection, radiofrequency ablation, and transcatheter arterial chemoembolization (TACE) are not considered as a curative treatment and have achieved very limited success in eradicating large HCC. With the development of new radiotherapy (RT) technique, RT can be more safely given to patients with larger tumor burden. Thus, TACE combined with RT has been suggested for treating large HCC. Based on the results of these studies, RT could achieve a tumor response rate of 50 % to 70 %. However, it has not been definitively shown to prolong the overall or disease-free survival due to lack of a phase III clinical trial. In contrast, a retrospective clinical investigation with molecular study suggests that sublethal dose of RT promoted HCC growth outside RT field.

Two phase III trials were shown to be efficacious and well-tolerated in patients with advanced HCC. Median overall survival was significantly 2 to 3 months longer in the sorafenib group than that in the placebo. It is interesting to recognize the combined therapeutic effect of RT with sorafenib. Based on several preclinical experiments, tumor angiogenesis inhibitors seem to be synergistic with irradiation when using before RT, concurrently with RT, or after RT. Thus, we design a single-arm phase II clinical trial to investigate the efficacy of combined RT with sorafenib.

The eligibility criteria are patients with unresectable HCC; good performance status; no prior radiotherapy for the liver; clinical measurable tumor; good liver function and good compliance. After entering this study, the testee will receive RT to hepatic tumor with concurrently sorafenib with a dose of 400 mg twice daily. Hepatic RT will be performed with a daily fraction size of 2.0 to 2.5 Gy to a total dose of 46 Gy to 60 Gy. After RT, maintenance sorafenib with a dose of 400 mg twice daily will be ongoing. Sorafenib will be continued until the occurrence of clinical or radiologic progression, or the occurrence of either unacceptable adverse events or death. Minimum maintenance duration of 6 months is recommended, but not mandatory. The primary end points are response rate and toxicities profile. The secondary endpoints are time to radiological progression interval (TRPI), overall survival, and quality of life assessment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 69 Years

Eligibility

Inclusion Criteria:

1. Patients with unresectable hepatoma with transarterial embolization (TAE) failure or who are not suitable for TAE.

2. Age: 20 ~ 69 years.

3. ECOG 0 or 1.

4. Life expectancy of at least 12 weeks.

5. Child-Pugh A or B (preferentially score ? 7).

6. Cancer of the Liver Italian Program (CLIP) score ? 3.

7. Pretreatment liver function test and renal function test:

• Total bilirubin < 1.5 times the upper limit of normal (ULN)? 3.0(ULN)in patients treated by biliary drainage for obstructive jaundice.

• GOP/GPT ? 5 X of upper limit of normal range.

• Alkaline phosphatase ? 4X of upper limit of normal range.

• Prothrombin time/partial prothrombin time < 1.5 X of ULN.

• Serum Creatinine ? 1.0 x ULN.

8. Pretreatment blood count:

• Hemoglobulin ? 9 g/dl.

• Absolute neutrophil count ? 1500/mm3.

• Platelet count ? 100,000/mm3.

9. Subjects with at least one uni-dimensional or bi-dimensional measurable lesion. Lesion must be measured by CT scan or MRI.

10. Patients must fully recover from prior therapy that given > 4 weeks before enrolment.11. Signed informed consent must be obtained prior to any study related procedures.

Exclusion Criteria:

1. Child-Pugh C

2. CLIP score ? 4

3. Patients with evidence of extrahepatic or metastatic disease

4. Patients with evidence of massive ascites

5. Patients receiving previous irradiation to liver

6. Patients with previous use of Thalidomide less than 6 months from entering of the study

7. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted)

8. Active clinically serious infections ( > grade 2 CTC version 2)

9. Patients undergoing renal dialysis

10. Patients with evidence or history of bleeding diathesis

11. Prior treatment with EGFR TKIs or VEGFR TKIs

12. Hypertension uncontrolled by medical therapy

13. Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper.

14. Chemotherapy or immunotherapy or other systemic anti-cancer therapy within 4 weeks (6 weeks for nitrosoureas, mitomycin and suramin)

15. Major surgery within 4 weeks of start of study

16. Concomitant treatment with strong CYP3A4 inducers or inhibitors

17. Investigational drug therapy outside of this trial during or within 4 weeks of study entry

18. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.

19. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 days period after last study drug dosing.

20. Pregnant or breast-feeding patients

21. Known or suspected allergy to the investigational agent or any agent given in association with this trial

22. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry

23. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study

24. Patients with seizure disorder requiring medication

25. History of organ allograft

26. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry

27. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

28. Autologous bone marrow transplant or stem cell rescue within 4 months of study

29. Patients unable to swallow oral medications

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Other:
• Radiotherapy combined with sorafenib
Radiotherapy: 46 Gy to 60 Gy prescribed to involved hepatic tumor Sorafenib: 2 tablet of sorafenib (200mg) twice daily (totally 800mg per day)

Locations

Country	Name	City	State
Taiwan	Chi-Mei Hospital	Tainan
Taiwan	Taipei Medical University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	Response rate at 1-month and 6-month after radiotherapy.; Toxicities profile of combinede treatment	1-month and 6-month response rate	Yes
Secondary	Time-to radiological progression interval	Time-to radiological progression interval; 2-year overall survival; 2-year progression-free survival; Quality of life	2-years	Yes