Sorafenib With or Without Gemcitabine and Oxaliplatin in Treating Patients With Locally Advanced, Unresectable, or Metastatic Liver Cancer

NCT00941967 | Completed Phase 2

• 5 other identifiers: CDR0000638394CLCC-GONEXT-PRODIGE-10VA 2007/40INCA-RECF0917EUDRACT-2008-000123-26
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether sorafenib tosylate is more effective when given with or without gemcitabine hydrochloride and oxaliplatin in treating patients with liver cancer. PURPOSE: This randomized phase II trial is studying sorafenib tosylate to see how well it works when given with or without gemcitabine hydrochloride and oxaliplatin in treating patients with locally advanced, unresectable, or metastatic liver cancer.

Conditions

Liver Cancer

Keywords

adult primary hepatocellular carcinoma; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; advanced adult primary liver cancer

Outcome Measures

Primary Outcomes (2)

• Tumor response according to RECIST criteria

  18 months

• Progression-free survival

  18 months

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive oral sorafenib tosylate as in arm I. Patients also receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment with gemcitabine hydrochloride and oxaliplatin repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: sorafenib tosylate

Arm II

EXPERIMENTAL

Patients receive oral sorafenib tosylate twice daily on days 1-14.

Drug: gemcitabine hydrochloride; Drug: oxaliplatin; Drug: sorafenib tosylate

Interventions

gemcitabine hydrochloride DRUG

Given IV

Arm II

oxaliplatin DRUG

Given IV

Arm II

sorafenib tosylate DRUG

Given orally.

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed hepatocellular carcinoma not amenable to liver transplantation * Locally advanced, unresectable, or metastatic disease * At least 1 lesion accurately measured in ≥ 1 dimension according to RECIST criteria AND has not been previously treated with local therapy (e.g., intra-arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) * No presence of bone metastasis only * No known brain metastasis PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Life expectancy \> 12 weeks * ANC \> 1,500/mm\^3 * WBC \> 3,000/mm\^3 * Platelet count ≥ 90,000/mm\^3 * Hemoglobin \> 10 g/dL * Total protein ≥ 40% * ALT or AST ≤ 1.5 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN * Amylase and lipase \< 1.5 times ULN * Creatinine \< 1.5 times ULN * Creatinine clearance ≥ 60 mL/min * Albumin ≥ 2.8 mg/dL * INR ≤ 2.3 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during study and for up to 4 months for females and 6 months for males after completion of study treatment * CLIP score 0-3 * No Child Pugh score B or C cirrhosis * No known HIV positivity * No other prior malignancy, except adequately treated or curative basal cell skin cancer or carcinoma in situ of the cervix * No known or suspected allergy to the investigational agent or any agent given in association with this study * No cardiovascular disease, including any of the following: * Cardiac arrhythmia requiring antiarrhythmic therapy, except beta-blockers or digoxin for chronic atrial fibrillation * Active coronary artery disease or ischemia * Myocardial infarction within the past 6 months * NYHA class II-IV congestive heart failure * No uncontrolled hypertension * No severe active bacterial or fungal infection \> CTCAE v3.0 grade 2 * No peripheral neuropathy ≥ grade 2 * No condition that could affect the absorption of study drug, including any of the following: * Malabsorption syndrome * Disease significantly affecting gastrointestinal function * Bowel obstruction or sub-obstruction * No dysphagia or inability to swallow tablets * No history of seizures requiring long-term antiepileptic treatment * No unstable condition that would jeopardize safety or compliance with study including any of the following : * Medical, psychological, or social conditions * Substance abuse * Legal incapacity or limited legal capacity * No psychological, familial, social, or geographic reasons that would preclude clinical follow-up * Must be registered in a social security program PRIOR CONCURRENT THERAPY: * No prior organ transplantation with immunosuppressive treatment * No prior systemic chemotherapy or systemic antiangiogenic treatment for hepatocellular carcinoma * No prior major resection of the stomach or proximal small bowel * Prior anticoagulation therapy (e.g., warfarin or heparin) allowed with INR parameters within normal limit range * At least 4 weeks since prior local therapy to lesions and treated lesions may not be selected as target lesions * No concurrent or prior long-term treatment with CYP3A4 inducers (e.g., rifampin, hypericum perforatum, phenytoin, carbamazepine, phenobarbital, and dexamethasone) * No concurrent antitumoral treatment, including tamoxifen, interferon, or somatostatin analogues * No other concurrent experimental drugs or anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (1)

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34295, France

Location

Related Publications (8)

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  PMID: 10655437 BACKGROUND

• Blay JY, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, Emile JF, Gronchi A, Hogendoorn PC, Joensuu H, Le Cesne A, McClure J, Maurel J, Nupponen N, Ray-Coquard I, Reichardt P, Sciot R, Stroobants S, van Glabbeke M, van Oosterom A, Demetri GD; GIST consensus meeting panelists. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol. 2005 Apr;16(4):566-78. doi: 10.1093/annonc/mdi127.

  PMID: 15781488 BACKGROUND

• Blay JY, Landi B, Bonvalot S, Monges G, Ray-Coquard I, Duffaud F, Bui NB, Bugat R, Chayvialle JA, Rougier P, Bouche O, Bonichon F, Lassau N, Vanel D, Nordlinger B, Stoeckle E, Meeus P, Coindre JM, Scoazec JY, Emile JF, Ranchere D, Le Cesne A. [Recommendations for the management of GIST patients]. Bull Cancer. 2005 Oct;92(10):907-18. French.

  PMID: 16266874 BACKGROUND

• Lassau N, Lamuraglia M, Leclere J, Rouffiac V. [Functional and early evaluation of treatments in oncology: interest of ultrasonographic contrast agents]. J Radiol. 2004 May;85(5 Pt 2):704-12. doi: 10.1016/s0221-0363(04)97651-2. French.

  PMID: 15238871 BACKGROUND

• Lassau N, Chami L, Peronneau P. [Current events about echography in 2006: position of the ultrasound functional imaging for the early evaluation of targeted therapeutics]. Bull Cancer. 2006 Dec;93(12):1207-11. French.

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• Lassau N, Lamuraglia M, Chami L, Leclere J, Bonvalot S, Terrier P, Roche A, Le Cesne A. Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography. AJR Am J Roentgenol. 2006 Nov;187(5):1267-73. doi: 10.2214/AJR.05.1192.

  PMID: 17056915 BACKGROUND

• Lamuraglia M, Escudier B, Chami L, Schwartz B, Leclere J, Roche A, Lassau N. To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound. Eur J Cancer. 2006 Oct;42(15):2472-9. doi: 10.1016/j.ejca.2006.04.023. Epub 2006 Sep 11.

  PMID: 16965911 BACKGROUND

• Escudier B, Lassau N, Angevin E, Soria JC, Chami L, Lamuraglia M, Zafarana E, Landreau V, Schwartz B, Brendel E, Armand JP, Robert C. Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma. Clin Cancer Res. 2007 Mar 15;13(6):1801-9. doi: 10.1158/1078-0432.CCR-06-1432.

  PMID: 17363536 BACKGROUND

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Gemcitabine; Oxaliplatin; Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Eric Assenat, MD

  Hopital Saint Eloi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2009
• First Posted: July 20, 2009
• Study Start: December 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2012
• Last Updated: July 10, 2019

Record last verified: 2017-08

Locations

FR (1)