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Sponsored by: |
Italian Trial in Medical Oncology |
Information provided by: | Italian Trial in Medical Oncology |
ClinicalTrials.gov Identifier: | NCT00619541 |
To use Sorafenib + 5-FU for evaluate activity, efficacy, safety, PD and PK in patients with advanced HCC
Condition | Intervention | Phase |
Hepatocellular Carcinoma |
Drug: Sorafenib and Infusional 5-Fluorouracil |
Phase II |
MedlinePlus related topics: | Cancer Liver Cancer |
ChemIDplus related topics: | Sorafenib Sorafenib tosylate Fluorouracil |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study |
Official Title: | Phase II Study of Bay 43-9006 and Infusional 5-Fluorouracil in Advanced Hepatocellular Carcinoma. |
Estimated Enrollment: | 46 |
Study Start Date: | January 2007 |
Estimated Study Completion Date: | November 2007 |
Primary Completion Date: | November 2007 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
A,: Experimental
5-FU 3000 mg/sqm 48 hours continuous infusion every 14 days Bay 400 mg bid orally continuously 5-FU will be administered for a maximum of 12 cycles. Bay 43-9006 will be administered from the start of treatment in combination with 5-FU until progression of disease.
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Drug: Sorafenib and Infusional 5-Fluorouracil
5-FU 3000 mg/sqm 48 hours continuous infusion every 14 days Bay 400 mg bid orally continuously 5-FU will be administered for a maximum of 12 cycles. Bay 43-9006 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.
Bay 43-9006 (Bay) 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 Bay administerd 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 Bay 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.
Bay as single agent in HCC has demonstrated activity in terms of objective responses and promising duration of stable disease.
The combination of Bay 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 Bay 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 Bay 400 mg bid orally continuously 5-FU will be administered for a maximum of 12 cycles. Bay 43-9006 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:
Other Exclusion Criteria:
Contact: Ricci Sergio, MD | +39 050 992145 | sergio.ricci@ao-pisa.toscana.it |
Contact: Orlandini Cinzia, phD | +39 050 993173 | c.orlandini@med.unipi.it |
Italy | |||||
Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina ... Indirizzo: via Roma, 55 - 56100 Pisa Tel. 050-2218690 - Fax. 050-2218685 | Recruiting | ||||
Pisa, Italy, 56100 | |||||
Contact: Orlandini Cinzia, phD +39 050 992145 c.orlandini@med.unipi.it | |||||
Principal Investigator: Ricci Sergio, MD |
Italian Trial in Medical Oncology |
Responsible Party: | Bayer Schering Pharma Italy ( Bayer Schering Pharma ) |
Study ID Numbers: | GAODUE |
First Received: | February 11, 2008 |
Last Updated: | May 27, 2008 |
ClinicalTrials.gov Identifier: | NCT00619541 |
Health Authority: | Italy: Ethics Committee |
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