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Trial · Interventional

CompletedPhase 2/3Registry data

GH, IGF-I and Somatostatin Analogues in Hepatocellular Carcinoma

Short name SS-HCC

NCTNCT00495846 (opens ClinicalTrials.gov in a new tab)Other idNeuroendoUnit-4
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2/3
Enrollment
25 participants (actual)
Sponsor
Federico II University · Other
Design
Not randomized · Open label (no masking)
Countries
1 country

Italy

Start
Apr 2007
Primary completion
Apr 2008
Completion
Dec 2008
First posted
3 Jul 2007 (estimated)
Last update posted
17 Aug 2009 (estimated)
Conditions
Advanced Hepatocellular Carcinoma

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
200720082009
  1. Ph 2/3

    SS-HCC

    NCT00495846

    Apr 2007 to Dec 2008

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Octreotide-LAR, Lanreotide AutogelDrug
  • Locoregional treatmentsOther

Arms2

  • 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

  • Other

    B

    Historical controls

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Prolongation of the survival curve (>6 months)

    Time frame · 12 months

Secondary outcomes(2)

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

    Time frame · 12 months

  2. Improvement of quality of life according with SF36 questionnaire

    Time frame · 12 months

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies5

Studies that cite this trial.

Studies with results

1 study on this page

PubMed tag: none · 2000

12 results

Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo.

Raderer et al. 2000International journal of oncologycited by 47

PMID 10811995DOI 10.3892/ijo.16.6.1197PUB-10811995

Full text at the publisher12 results
Publisher pageSee results (12)

More studies

4 studies on this page

Indexing hint: Randomized controlled trial · 2007

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial.

Dimitroulopoulos et al. 2007World journal of gastroenterologycited by 44

PMID 17589893PMC4436600DOI 10.3748/wjg.v13.i23.3164PUB-17589893

Rights unknown
Source link

Indexing hint: Clinical trial · 2006

Corrected

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Cebon et al. 2006British journal of cancercited by 42

PMID 16953241PMC2360532DOI 10.1038/sj.bjc.6603325PUB-16953241

CC BY
Download PDFRead the notice

Indexing hint: Randomized controlled trial · 2002

Corrected

A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma.

Yuen et al. 2002Hepatology (Baltimore, Md.)cited by 120

PMID 12198662DOI 10.1053/jhep.2002.35071PUB-12198662

Rights unknown
Source linkRead the notice

Indexing hint: Case report · 1999

Successful treatment of an advanced hepatocellular carcinoma with the long-acting somatostatin analog lanreotide.

Raderer et al. 1999The American journal of gastroenterologycited by 9

PMID 9934776DOI 10.1111/j.1572-0241.1999.00821.xPUB-09934776

Full text at the publisher
Publisher page

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultLlovet JM, Beaugrand M. Hepatocellular carcinoma: present status and future prospects. J Hepatol. 2003;38 Suppl 1:S136-49. doi: 10.1016/s0168-8278(02)00432-4. No abstract available. PMID 12591191
  • ResultBlanc P, Desprez D, Fabre JM, Pageaux G, Daures JP, Larrey D, Saint-Aubert B, Michel H, Maurel P. Contribution of primary cultures of adult human hepatocytes to the pathophysiology of hepatocellular carcinoma. J Hepatol. 1996 Nov;25(5):663-9. doi: 10.1016/s0168-8278(96)80236-4. PMID 8938543
  • ResultBurr AW, Hillan KJ, McLaughlin KE, Ferrier R, Chapman C, Mathew J, Burt AD. Hepatocyte growth factor levels in liver and serum increase during chemical hepatocarcinogenesis. Hepatology. 1996 Nov;24(5):1282-7. doi: 10.1002/hep.510240549. PMID 8903411
  • ResultTomiya T, Fujiwara K. Serum transforming growth factor alpha level as a marker of hepatocellular carcinoma complicating cirrhosis. Cancer. 1996 Mar 15;77(6):1056-60. doi: 10.1002/(sici)1097-0142(19960315)77:63.0.co;2-f. PMID 8635123
  • ResultJones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995 Feb;16(1):3-34. doi: 10.1210/edrv-16-1-3. No abstract available. PMID 7758431
  • ResultChan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998 Jan 23;279(5350):563-6. doi: 10.1126/science.279.5350.563. PMID 9438850
  • ResultHankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998 May 9;351(9113):1393-6. doi: 10.1016/S0140-6736(97)10384-1. PMID 9593409
  • ResultGiovannucci E, Pollak M, Platz EA, Willett WC, Stampfer MJ, Majeed N, Colditz GA, Speizer FE, Hankinson SE. Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and the risk of colorectal adenoma and cancer in the Nurses' Health Study. Growth Horm IGF Res. 2000 Apr;10 Suppl A:S30-1. doi: 10.1016/s1096-6374(00)90014-5. No abstract available. PMID 10984283
  • ResultNardone G, Romano M, Calabro A, Pedone PV, de Sio I, Persico M, Budillon G, Bruni CB, Riccio A, Zarrilli R. Activation of fetal promoters of insulinlike growth factors II gene in hepatitis C virus-related chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatology. 1996 Jun;23(6):1304-12. doi: 10.1002/hep.510230602. PMID 8675143
  • ResultYang D, Faris R, Hixson D, Affigne S, Rogler CE. Insulin-like growth factor II blocks apoptosis of N-myc2-expressing woodchuck liver epithelial cells. J Virol. 1996 Sep;70(9):6260-8. doi: 10.1128/JVI.70.9.6260-6268.1996. PMID 8709253
  • ResultBuzzelli G, Dattolo P, Pinzani M, Brocchi A, Romano S, Gentilini P. Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm. Am J Gastroenterol. 1993 Oct;88(10):1744-8. PMID 8213718
  • ResultMattera D, Capuano G, Colao A, Pivonello R, Manguso F, Puzziello A, D'Agostino L. Increased IGF-I : IGFBP-3 ratio in patients with hepatocellular carcinoma. Clin Endocrinol (Oxf). 2003 Dec;59(6):699-706. doi: 10.1046/j.1365-2265.2003.01909.x. PMID 14974910
  • ResultLlovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999 Dec;30(6):1434-40. doi: 10.1002/hep.510300629. PMID 10573522
  • ResultLlovet JM, Fuster J, Bruix J; Barcelona-Clinic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004 Feb;10(2 Suppl 1):S115-20. doi: 10.1002/lt.20034. PMID 14762851
  • ResultLivraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology. 1999 Mar;210(3):655-61. doi: 10.1148/radiology.210.3.r99fe40655. PMID 10207464
  • ResultLivraghi T, Giorgio A, Marin G, Salmi A, de Sio I, Bolondi L, Pompili M, Brunello F, Lazzaroni S, Torzilli G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology. 1995 Oct;197(1):101-8. doi: 10.1148/radiology.197.1.7568806. PMID 7568806
  • ResultLencioni RA, Allgaier HP, Cioni D, Olschewski M, Deibert P, Crocetti L, Frings H, Laubenberger J, Zuber I, Blum HE, Bartolozzi C. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003 Jul;228(1):235-40. doi: 10.1148/radiol.2281020718. Epub 2003 May 20. PMID 12759473
  • ResultKouroumalis E, Samonakis D, Skordilis P. Octreotide treatment of hepatocellular carcinoma. Hepatology. 2003 Feb;37(2):477. doi: 10.1053/jhep.2003.50026. No abstract available. PMID 12540801
  • ResultSamonakis DN, Moschandreas J, Arnaoutis T, Skordilis P, Leontidis C, Vafiades I, Kouroumalis E. Treatment of hepatocellular carcinoma with long acting somatostatin analogues. Oncol Rep. 2002 Jul-Aug;9(4):903-7. PMID 12066229
  • ResultKapadia CR. Somatostatin and hepatocellular carcinoma. Gastroenterology. 1998 Nov;115(5):1298-9. doi: 10.1016/s0016-5085(98)70109-x. No abstract available. PMID 9797392

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 75 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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