Clinical trial NCT00155272: Radiotherapy Plus Thalidomide in Locally Advanced Hepatocellular Carcinoma
Official title: A Pilot Clinical and Mechanistic Study of Radiotherapy Plus Thalidomide in Locally Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Radiotherapy
Thalidomide
Dynamic contrast enhanced MRI
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Health Research Institutes, Taiwan
First posted: 2005-09-12
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a pilot study of concomitant radiotherapy and thalidomide for patients with locally advanced HCC.Besides toxicity and efficacy, mechanistic studies including dynamic contrast enhanced MRI and serum cytokines will be evaluated.

Detailed description: This is a pilot study of concomitant radiotherapy and thalidomide for patients with locally advanced HCC. Patients whose tumor(s) are not suitable for other local treatment, such as surgery, trans-arterial chemoembolization (TAE), ethanol injection, or radiofrequency ablation. will be enrolled.Radical radiotherapy will be started after pre-treatment evaluation. The total dose of RT will be 50Gy in 25 fractions to local tumor(s). Oral Thalidomide will be started 3 days before RT begins. Thalidomide treatment will continue for totally 6 months or until tumor progression. Dynamic contrast enhanced MRI (DCEMRI) will be done at the following time points to assess the change in tumor perfusion: (1) before the start of thalidomide treatment; (2) 3 days after thalidomide before radiotherapy; (3) 2weeks after radiotherapy begins;and (4) 1 month after radiotherapy completes. DCEMRI will then be done every 3 months until disease progression.Serum samples for angiogenic cytokine studies will also be collected.The study was designed to evaluate the feasibility and tolerability of combination treatment of radiotherapy and thalidomide for locally advanced HCC. The sample size was determined by the expected incidence of grade 4 toxicity of the combination treatment versus radiotherapy alone for locally advanced HCC. Since the grade 4 toxicity of radiotherapy alone is 7-9%, we need at least 15 patients to evaluate for feasibility of the combination treatment. With an estimated drop out rate of approximately 10%, 17 patients will be enrolled.

Eligibility criteria: Inclusion Criteria:

* 1.1 Patients with measurable, locally advanced HCC that are not suitable for other local therapies, including surgery, TAE, alcohol injection, or radiofrequency ablation.

1.2 Patients with histological confirmed HCC or patients who do not have histological diagnosis but have met all of the following criteria: 1.2.1 Presence of chronic viral hepatitis and/or cirrhosis 1.2.2 Presence of hepatic tumor(s) with image findings (sonography, CT scan) compatible with HCC.

1.2.3 A persistent elevation of serum a-fetoprotein level ³ 400 ng/ml without any evidence of ana-fetoprotein-secreting germ cell tumor.

1.3 Patients without any local or systemic therapy for HCC within 4 weeks. 1.4 Patients with age \> 20 years and \< 70 years. 1.5 Patients with a performance status of ECOG score \< 1. 1.6 Patients must fulfill all of the following criteria: 1.6.1 Child-Pugh's Score ≦ 7. 1.6.2 Serum total bilirubin \< 1.5 times upper normal limit (UNL 1.6.3 Serum alanine transaminase (ALT) \< 5 times UNL 1.6.4 Platelet count \> 5.0 x 104 / mm3. 1.6.5 White blood cell count \> 3,000 / mm3. 1.6.6 Serum creatinine \< 2.0 mg/dL 1.7 Patient must have local tumors less than one half of the whole liver and the tumors can be encompassed within RT fields 1.8 Signed informed consent 1.9 Sexually active patients, in conjunction with their partner, must practice birth control during, and for 2 months after, thalidomide therapy.

1.10 Female patients in child-bearing age must have negative pregnancy test.

Exclusion Criteria:

* 2.1. Patients with documented extrahepatic metastasis. 2.2. Patients who received previous radiotherapy to abdominal area. 2.3. Patients who have received thalidomide treatment prior to enrollment. 2.4. Patients who had other investigational drug treatment within 4 weeks prior to enrollment.

2.5. Patients with NCI grade 2 or greater peripheral neuropathy of any causes. 2.6. Patients with other systemic diseases that required concurrent usage of glucocorticosteroid or immunosuppressant agent(s).

2.7. Patients who have major systemic diseases that the attending physicians consider inappropriate for radiotherapy or thalidomide therapy.

Primary outcomes:
measure: The primary endpoint is the feasibility and tolerability of thalidomide plus radiotherapy.
Secondary outcomes:
measure: The secondary end point is correlation of parameters of tumor perfusion assessed by DCEMRI and serum cytokine levels with objective tumor response.
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: NTUH
Study officials:
affiliation: National Health Research Institutes, Division of Cancer Research
name: Hui-Ju Ch'ang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Chih-Hung Hsu, M.D.
role: STUDY_CHAIR
affiliation: National Taiwan University Hospital
name: Tiffany Ting Fang Shih, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liang PC, Ch'ang HJ, Hsu C, Chen LT, Shih TT, Liu TW. Perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging predict outcomes of hepatocellular carcinoma receiving radiotherapy with or without thalidomide. Hepatol Int. 2015 Apr;9(2):258-68. doi: 10.1007/s12072-014-9557-1. Epub 2014 Jul 26.
citation: Ch'ang HJ, Hsu C, Chen CH, Chang YH, Chang JS, Chen LT. Phase II study of concomitant thalidomide during radiotherapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):817-25. doi: 10.1016/j.ijrobp.2010.10.067. Epub 2011 Jan 27.