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Sponsored by: |
Italian Trial in Medical Oncology |
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Information provided by: | Italian Trial in Medical Oncology |
ClinicalTrials.gov Identifier: | NCT00619541 |
The purpose of this study is to use Sorafenib + 5-FU to evaluate activity, efficacy, safety, pharmacodynamics (PD) and pharmacokinetics (PK) in patients with advanced hepatocellular carcinoma (HCC).
Condition | Intervention | Phase |
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Hepatocellular Carcinoma |
Drug: Infusional 5-Fluorouracil Drug: Sorafenib (Bay 43-9006) |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study |
Official Title: | Phase II Study of Sorafenib (Bay 43-9006) and Infusional 5-Fluorouracil in Advanced Hepatocellular Carcinoma. |
Estimated Enrollment: | 46 |
Study Start Date: | January 2007 |
Study Completion Date: | January 2009 |
Primary Completion Date: | November 2007 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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A: Experimental
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Drug: Infusional 5-Fluorouracil
5-FU 3000 mg/sqm 48 hours continuous infusion every 14 days. 5-FU will be administered for a maximum of 12 cycles.
Drug: Sorafenib (Bay 43-9006)
Sorafenib 400 mg bid orally continuously. Sorafenib will be administered from the start of treatment in combination with 5-FU until progression of disease.
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Numerous chemotherapeutic regimens have been tested for use against hepatocellular carcinoma (HCC). HCC is, however, highly resistant to chemotherapy; doxorubicin and 5- fluorouracil containing regimens, alone or in combinations, results in less than a 20% response, with a median survival of less than 4 months. Furthermore even the objective responses are short-lasting. In a metaanalysis of the published randomized studies on HCC, neither doxorubicin nor any chemotherapeutic agent has been shown to have any survival benefit for HCC patients. Sorafenib (Bay 43-9006) is a novel signal transduction inhibitor that prevent tumor cell proliferation and angiogenesis through blockade of the Raf/Mek/Erk pathway at the level of Raf Kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-beta. Recent preclinical studies have shown the activation of Mek-1/2 and its downstream target MAPK in HCC tumors. In a phase II study 137 patients advanced primary liver cancer with have been treated with Sorafenib administered as a single agent. Investigators reported seven patients with partial responses, five minor responses and 59 with stable disease for at least 4 months. Median overall survival was 9.2 months and median time to progression 4.2 months. This study showed that Sorafenib was well tolerated and side-effects were manageable and reversible.
Rationale
5-Fluorouracil (5-FU) is a widely used agent for patients with unresectable advanced HCC, with objective responses rates around 10%. Compared to bolus administration, infusional 5-FU in metastatic colorectal cancers has demonstrated increased activity with less toxicity. Sorafenib as single agent in HCC has demonstrated activity in terms of objective responses and promising duration of stable disease. The combination of Sorafenib and 5-FU was evaluated in a phase I study where the drug is associated with different 5FU based schedules with good toxicity profile and objectives responses in particular in colorectal carcinoma. Based on these data our purpose is to study infusional 5-FU with Sorafenib to evaluate the activity, efficacy, safety, pharmacokinetics and pharmacodynamics of this combination.
Study design and duration of treatment
5-FU 3000 mg/sqm 48 hours continuous infusion every 14 days Sorafenib 400 mg bid orally continuously 5-FU will be administered for a maximum of 12 cycles. Sorafenib will be administered from the start of treatment in combination with 5-FU until progression of disease.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Screening must be done within 28 days of study drug administration (laboratory evaluations must be done within 7 days). For inclusion in the study, patients must fulfill all of the following criteria:
Patients should have proven primary HCC according to one of the following criteria:
Adequate bone marrow, liver and renal function, as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
Exclusion Criteria:
Patients who meet the following criteria at the time of screening will be excluded; excluded medical conditions:
Excluded therapies and medications, previous and concomitant:
Anticancer therapy is defined as any agent or combination of agents with clinically proven anticancer activity administered systemically, with the purpose of affecting the cancer, either directly or indirectly, including palliative and therapeutic endpoints. In certain cases, local anticancer therapy is allowed. See Inclusion Criteria for details.
Other Exclusion Criteria:
Italy | |
Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina ... Indirizzo: via Roma, 55 - 56100 Pisa Tel. 050-2218690 - Fax. 050-2218685 | |
Pisa, Italy, 56100 |
Study ID Numbers: | PISADUE |
Study First Received: | February 11, 2008 |
Last Updated: | February 25, 2009 |
ClinicalTrials.gov Identifier: | NCT00619541 History of Changes |
Health Authority: | Italy: Ethics Committee |
HCC Sorafenib Pisa Ricci |
5-FU 5FU 5 FU Advanced HCC |
Antimetabolites Liver Diseases Digestive System Neoplasms Immunologic Factors Carcinoma, Hepatocellular Protein Kinase Inhibitors Immunosuppressive Agents Carcinoma |
Liver Neoplasms Digestive System Diseases Fluorouracil Gastrointestinal Neoplasms Adenocarcinoma Hepatocellular Carcinoma Sorafenib Neoplasms, Glandular and Epithelial |
Antimetabolites Liver Diseases Antimetabolites, Antineoplastic Neoplasms by Histologic Type Digestive System Neoplasms Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Carcinoma, Hepatocellular Physiological Effects of Drugs Enzyme Inhibitors Protein Kinase Inhibitors |
Immunosuppressive Agents Pharmacologic Actions Carcinoma Liver Neoplasms Neoplasms Neoplasms by Site Digestive System Diseases Therapeutic Uses Fluorouracil Adenocarcinoma Sorafenib Neoplasms, Glandular and Epithelial |