GH, IGF-I and Somatostatin Analogues in Hepatocellular Carcinoma (SS-HCC)
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| ClinicalTrials.gov Identifier: NCT00495846 |
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Recruitment Status :
Completed
First Posted : July 3, 2007
Last Update Posted : August 17, 2009
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The hepatocellular carcinoma (HCC) represents more than 5% of all human malignancies, with more than 500,000 deaths per year (1). In Campania region, mortality for HCC is 2 times higher than in the rest of Italy because of a higher locally prevalence of hepatitis-C virus infection.
Development of HCC in liver cirrhosis is associated with increased DNA synthesis and regeneration of hepatocytes (2). Hepatocyte growth factor, the transforming growth factor-α, the fibroblast growth factor are well studied (3,4) while the insulin-like growth factor system (IGF-I, IGF-II and their binding proteins) has been less investigated. IGF-I and IGF-II modulate growth, metabolism and cell differentiation and have specific receptors in the liver (5). IGF-I levels in the upper normal range have been associated with an increased risk to develop prostate cancer (6), breast cancer (7) and colon cancer (8). Some data report increased expression of IGF-II in HCC (9,10) and others suggest a role of increased IGF-I bioavailability in HCC (11). We reported increased IGF-I/IGFBP-3 ratio in patients with HCC compared with those with cirrhosis with a similar liver function, so suggesting increased IGF-I bioavailability in HCC (12).
There is no currently medical treatment for patients with advanced HCC which has a very poor prognosis (survival <6 months). Because of limited liver function, classical chemotherapy cannot be applied (13). In patients with HCC without cirrhosis, surgery is possible only in 5% while in those with cirrhosis first-line treatment is still questioned as survival is <50% three years after operation. Patients suitable for local resection of HCC are only those with Child-Pugh's "hyper A" liver function class, who are a minority (14-16). Percutaneous resection treatments may treat approximately 70%-90% of tumors with maximal diameters of <3 cm (15,17-19).
Somatostatin analogues are indicated in patients with neuroendocrine tumors expressing somatostatin receptors type 2 and 5 and has excellent safety profile. In advanced HCC, some studies demonstrated beneficial effects (20,21) while some others did not (22,23).
Only a few data are available on somatostatin receptor expression in HCC (24,25). Somatostatin analogues have also a clear-cut inhibitory effect on circulating IGF-I levels with a potential additional effect in delaying HCC progression.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Hepatocellular Carcinoma | Drug: Octreotide-LAR, Lanreotide Autogel Other: Locoregional treatments | Phase 2 Phase 3 |
Show Detailed Description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 25 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Treatment of Advanced Hepatocellular Carcinoma With Depot Somatostatin Analogues: a Pilot Prospective Study Based on Somatostatin Receptors Tumors Expression |
| Study Start Date : | April 2007 |
| Actual Primary Completion Date : | April 2008 |
| Actual Study Completion Date : | December 2008 |
| Arm | Intervention/treatment |
|---|---|
Experimental: A
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Drug: Octreotide-LAR, Lanreotide Autogel
Octreotide-LAR intramuscular, dose of 30 mg every 28 days to increase up to 60 mg; lanreotide autogel 120 mg deep subcutaneous every 28 days for 3 months then uptitrated according with the protocol.
Other Names:
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B
Historical controls
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Other: Locoregional treatments |
- Prolongation of the survival curve (>6 months) [ Time Frame: 12 months ]
- Improvement of liver function, Reduction of biological markers of disease (if elevated before starting the treatment) [ Time Frame: 12 months ]
- Improvement of quality of life according with SF36 questionnaire [ Time Frame: 12 months ]
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with cirrhosis without HCC in all liver function classes already receiving specific therapy for cirrhosis who accept be subjected to liver biopsy and to sign the written informed consent to participate to the study
- Patients with cirrhosis with multifocal HCC and clinical and/or radiological signs of persistence or recurrence of HCC in presence or absence of thrombosis of the portal vein, with a single nodule of > 6 cm in size or multiple nodules of > 3 cm in size who accept be subjected to liver biopsy and to sign the written informed consent to participate to the study
Exclusion Criteria:
- Age < 18 yrs or > 75 yrs
- Pregnancy or lactation
- Intolerance to somatostatin analogues
Treatment protocol:
- In all patients fulfilling the inclusion criteria, treatment will begin with octreotide-LAR at a dose of 30 mg every 28 days or lanreotide autogel 120 mg every 28 days for 3 months.
- After 28, 56 and 74 days (immediately before the next injection) all patients will be admitted to the Day Hospital of the IX Division of Internal Medicine of the D. Cotugno Hospital for the clinical examination, blood chemistry, blood sampling for the IGF axis analysis, and abdominal ultrasound. After 74 days, abdominal CT or MRI will also be performed.
- Then, in all survivors the interval between injection will be reduced to 21 days and follow up for the next 3 months will be done as stated before the day immediately preceding the injection.
- Then, in the subsequent follow-up the interval between injection will be reduced to 14 days and all procedures will be repeated at monthly intervals.
- All the patients fulfilling the inclusion criteria but refusing to participate to the study will be followed with the same methodology of those receiving the somatostatin analogues treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00495846
| Italy | |
| D. Cotugno Hospital | |
| Naples, Italy, 80131 | |
| Principal Investigator: | Annamaria Colao, MD, PhD | University Federico II of Naples |
Publications of Results:
| Responsible Party: | Annamaria Colao, Federico II U |
| ClinicalTrials.gov Identifier: | NCT00495846 History of Changes |
| Other Study ID Numbers: |
NeuroendoUnit-4 |
| First Posted: | July 3, 2007 Key Record Dates |
| Last Update Posted: | August 17, 2009 |
| Last Verified: | August 2009 |
Keywords provided by Federico II University:
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Hepatocellular carcinoma Somatostatin analogues Somatostatin receptors Octreotide |
Lanreotide IGF-I IGF-II |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Liver Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases |
Octreotide Lanreotide Angiopeptin Somatostatin Gastrointestinal Agents Antineoplastic Agents, Hormonal Antineoplastic Agents Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |