Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00154817
Status:
COMPLETED
Last Update Posted:
2005-11-22
First Post:
2005-09-08
Brief Title:
A Phase II Study of Radiotherapy for Locally Advanced Hepatocellular Carcinoma HCC
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
A Phase II Clinical and Mechanistic Study of Radiotherapy for Locally Advanced Hepatocellular Carcinoma
Status:
COMPLETED
Status Verified Date:
2002-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 This is a phase II study of radiotherapy for patients with locally advanced HCC
2 Patients whose tumors are not suitable for other local treatment such as surgery trans-arterial chemoembolization TAE ethanol injection or radiofrequency ablation will be enrolled
3 Radical radiotherapy will be started after pre-treatment evaluation The total dose of RT will be 50Gy in 25 fractions to local tumors
4 Dynamic contrast enhanced MRI and serum samples will be done at the following time points to assess the change in tumor perfusion 1 before the start of thalidomide treatment 2 2weeks after radiotherapy begins and 3 1 month after radiotherapy completes DCEMRI will then be done every 3 months until disease progression
5 The study was designed to evaluate the response rate and tolerability of radical radiotherapy for locally advanced HCC The sample size was determined by the expected incidence of grade 4 toxicity and response rate of radiotherapy for locally advanced HCC Since the grade 4 toxicity of radiotherapy alone is 10 the response rate is 60 we need at least 12 patients to evaluate for the treatment
2 Patients whose tumors are not suitable for other local treatment such as surgery trans-arterial chemoembolization TAE ethanol injection or radiofrequency ablation will be enrolled
3 Radical radiotherapy will be started after pre-treatment evaluation The total dose of RT will be 50Gy in 25 fractions to local tumors
4 Dynamic contrast enhanced MRI and serum samples will be done at the following time points to assess the change in tumor perfusion 1 before the start of thalidomide treatment 2 2weeks after radiotherapy begins and 3 1 month after radiotherapy completes DCEMRI will then be done every 3 months until disease progression
5 The study was designed to evaluate the response rate and tolerability of radical radiotherapy for locally advanced HCC The sample size was determined by the expected incidence of grade 4 toxicity and response rate of radiotherapy for locally advanced HCC Since the grade 4 toxicity of radiotherapy alone is 10 the response rate is 60 we need at least 12 patients to evaluate for the treatment
Detailed Description:
Hepatocellular carcinoma HCC is one of the most common malignancies in Asian countries Surgical resection is potentially the only form of curative treatment However less than 20 of patients are surgical candidates at diagnosis Nonsurgical treatment options include transcatheter arterial chemoembolization TACE percutaneous acetic acid or ethanol injection therapy and radio-frequency ablation They are sometimes unsatisfactory especially for patients with portal vein thrombosis or large infiltrative hepatic tumors Repeated treatments are often necessary
Radiotherapy RT for the treatment of HCC has been attempted for more than 4 decades Early trials adopted whole liver irradiation but used an inadequate radiation dose Because of the unsatisfactory results obtained with this low-dose whole liver irradiation RT has not long been considered for the treatment of HCC Recently local not whole liver RT has been attempted by several investigators who have shown that high doses of radiation can be safely delivered to a portion of the liver alone or in combination with other nonsurgical modalities Their results suggest that local RT can be an effective component of the treatment regimen for HCC
Development of surrogate markers to monitor the response of HCC to radiotherapy is important because of the following reasons First the response as evaluated by conventional imaging studies is usually slow and may be unreliable The maximal response to radiotherapy is often achieved 6 months after completion of radiotherapy The slow response to radiotherapy makes it difficult to modify an ineffective treatment regimen in a more timely fashion to HCC especially for patients with low serum a-fetal protein AFP Second intra-hepatic recurrence outside RT field is a common cause of RT treatment failure Nearly half of the patients recur after RT with lesions outside RT fields Inflammation and normal liver damage caused by RT may have deleterious effect on tumor control through the release of cytokines or angiogenic factors Therefore the biological consequence of RT in both the tumors and the non-tumor liver parenchyma shall be carefully evaluated
Dynamic contrast enhanced magnetic resonance imaging DCEMRI may assess hepatic perfusion parameters which correlate with the severity of cirrhosis and portal hypertension In cervical cancer DCEMRI enables us to evaluate the microcirculation of tumors as well as the blood perfusion of normal parenchyma Malignancy stage and prognosis have all been correlated with the enhancement parameters in cervical breast cancersSeveral studies have shown that successful therapies also result in changes in DCEMRI parameters which may prove to be a more accurate and earlier indication of response De Vries et al reported in rectal carcinoma patients receiving preoperative radiotherapy that perfusion index showed a significant increase in the 1st and 2nd week of treatment High perfusion index values correlated with greater lymph node down-staging Moffat et al also reported increased apparent diffusion coefficient ADC 3 weeks after the initiation of RT in brain cancer patients who had better local response Circulating angiogenic factors have been shown to provide important prognostic information about a variety of cancers 21 Elevated serum levels of VEGF or bFGF have been associated with increased invasiveness of HCC Placental growth factor PlGF a homolog of VEGF has been shown to have a synergistic effect with VEGF in pathologic angiogenesis such as angiogenesis induced by cancer or ischemia but its prognostic value in human cancers remains unclear
We would like to correlate functional image studies of blood flow and serum cytokines during radiotherapy with treatment outcome in hepatocellular carcinoma patients
Radiotherapy RT for the treatment of HCC has been attempted for more than 4 decades Early trials adopted whole liver irradiation but used an inadequate radiation dose Because of the unsatisfactory results obtained with this low-dose whole liver irradiation RT has not long been considered for the treatment of HCC Recently local not whole liver RT has been attempted by several investigators who have shown that high doses of radiation can be safely delivered to a portion of the liver alone or in combination with other nonsurgical modalities Their results suggest that local RT can be an effective component of the treatment regimen for HCC
Development of surrogate markers to monitor the response of HCC to radiotherapy is important because of the following reasons First the response as evaluated by conventional imaging studies is usually slow and may be unreliable The maximal response to radiotherapy is often achieved 6 months after completion of radiotherapy The slow response to radiotherapy makes it difficult to modify an ineffective treatment regimen in a more timely fashion to HCC especially for patients with low serum a-fetal protein AFP Second intra-hepatic recurrence outside RT field is a common cause of RT treatment failure Nearly half of the patients recur after RT with lesions outside RT fields Inflammation and normal liver damage caused by RT may have deleterious effect on tumor control through the release of cytokines or angiogenic factors Therefore the biological consequence of RT in both the tumors and the non-tumor liver parenchyma shall be carefully evaluated
Dynamic contrast enhanced magnetic resonance imaging DCEMRI may assess hepatic perfusion parameters which correlate with the severity of cirrhosis and portal hypertension In cervical cancer DCEMRI enables us to evaluate the microcirculation of tumors as well as the blood perfusion of normal parenchyma Malignancy stage and prognosis have all been correlated with the enhancement parameters in cervical breast cancersSeveral studies have shown that successful therapies also result in changes in DCEMRI parameters which may prove to be a more accurate and earlier indication of response De Vries et al reported in rectal carcinoma patients receiving preoperative radiotherapy that perfusion index showed a significant increase in the 1st and 2nd week of treatment High perfusion index values correlated with greater lymph node down-staging Moffat et al also reported increased apparent diffusion coefficient ADC 3 weeks after the initiation of RT in brain cancer patients who had better local response Circulating angiogenic factors have been shown to provide important prognostic information about a variety of cancers 21 Elevated serum levels of VEGF or bFGF have been associated with increased invasiveness of HCC Placental growth factor PlGF a homolog of VEGF has been shown to have a synergistic effect with VEGF in pathologic angiogenesis such as angiogenesis induced by cancer or ischemia but its prognostic value in human cancers remains unclear
We would like to correlate functional image studies of blood flow and serum cytokines during radiotherapy with treatment outcome in hepatocellular carcinoma patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None