GH, IGF-I and Somatostatin Analogues in Hepatocellular Carcinoma

NCT00495846 | Completed Phase 2 DMC

• 1 other identifier: NeuroendoUnit-4
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Somatostatin analogues; Somatostatin receptors; Octreotide; Lanreotide; IGF-I; IGF-II

Outcome Measures

Primary Outcomes (1)

• Prolongation of the survival curve (>6 months)

  12 months

Secondary Outcomes (2)

• Improvement of liver function, Reduction of biological markers of disease (if elevated before starting the treatment)

  12 months

• Improvement of quality of life according with SF36 questionnaire

  12 months

Study Arms (2)

A

EXPERIMENTAL

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

B

OTHER

Historical controls

Other: Locoregional treatments

Interventions

Octreotide-LAR, Lanreotide Autogel DRUG

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.

Also known as: Sandostatin-LAR, Ipstyl 120 mg, Somatuline Depot

A

Locoregional treatments OTHER

B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Age \< 18 yrs or \> 75 yrs
• Pregnancy or lactation
• Intolerance to somatostatin analogues
• Treatment protocol:
• 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.

Sponsors & Collaborators

• Federico II University: lead
• Ospedali dei Colli: collaborator

Study Sites (1)

D. Cotugno Hospital

Naples, 80131, Italy

Location

Related Publications (27)

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MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lanreotide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Annamaria Colao, MD, PhD

  University Federico II of Naples

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 2, 2007
• First Posted: July 3, 2007
• Study Start: April 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: December 1, 2008
• Last Updated: August 17, 2009

Record last verified: 2009-08

Locations

IT (1)