GH, IGF-I and Somatostatin Analogues in Hepatocellular Carcinoma (SS-HCC)

This study has been completed.
Sponsor:
Collaborator:
Azienda Ospedaliera "D Cotugno" Hospital of Infectious Diseases
Information provided by:
Federico II University
ClinicalTrials.gov Identifier:
NCT00495846
First received: July 2, 2007
Last updated: August 14, 2009
Last verified: August 2009
  Purpose

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 Intervention Phase
Advanced Hepatocellular Carcinoma
Drug: Octreotide-LAR, Lanreotide Autogel
Other: Locoregional treatments
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Federico II University:

Primary Outcome Measures:
  • Prolongation of the survival curve (>6 months) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement of liver function, Reduction of biological markers of disease (if elevated before starting the treatment) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Improvement of quality of life according with SF36 questionnaire [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: April 2007
Study Completion Date: December 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
  1. 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
  2. Patients with cirrhosis with multifocal HCC and clinical and/or radiological signs of persistence or recurrence of HCC in presence or absence of trombosis 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
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:
  • Sandostatin-LAR
  • Ipstyl 120 mg
  • Somatuline Depot
B
Historical controls
Other: Locoregional treatments

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00495846

Locations
Italy
D. Cotugno Hospital
Naples, Italy, 80131
Sponsors and Collaborators
Federico II University
Azienda Ospedaliera "D Cotugno" Hospital of Infectious Diseases
Investigators
Principal Investigator: Annamaria Colao, MD, PhD University Federico II of Naples
  More Information

Publications:
Cebon J, Findlay M, Hargreaves C, Stockler M, Thompson P, Boyer M, Roberts S, Poon A, Scott AM, Kalff V, Garas G, Dowling A, Crawford D, Ring J, Basser R, Strickland A, Macdonald G, Green M, Nowak A, Dickman B, Dhillon H, Gebski V; Australasian Gastro-Intestinal Trials Group (AGITG) Ag0001H Investigators. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide. Br J Cancer. 2006 Oct 9;95(7):853-61. Epub 2006 Sep 5. Erratum in: Br J Cancer. 2007 Apr 10;96(7):1154. Findlay, M [added]; Hargreaves, C [added]; Stockler, M [added]; Thompson, P [added]; Boyer, M [added]; Roberts, S [added]; Poon, A [added]; Scott, A M [added]; Kalff, V [added]; Garas, G [added]; Dowling, A [added]; Crawford, D [added]; Ring, J [added]; Basser, R [added]; Strickland, A [added]; Macdonald, G [added]; Green, M [added]; Nowak, A [added]; Dickman, B [added]; Dhillon, H [added]; Gebski, V [added].

Responsible Party: Annamaria Colao, Federico II U
ClinicalTrials.gov Identifier: NCT00495846     History of Changes
Other Study ID Numbers: NeuroendoUnit-4
Study First Received: July 2, 2007
Last Updated: August 14, 2009
Health Authority: Italy: Ministry of Health
Italy: National Institute of Health

Keywords provided by Federico II University:
Hepatocellular carcinoma
Somatostatin analogues
Somatostatin receptors
Octreotide
Lanreotide
IGF-I
IGF-II

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Somatostatin
Lanreotide
Angiopeptin
Octreotide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Cardiovascular Agents
Gastrointestinal Agents
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on October 19, 2014