The Effect of Sorafenib on Portal Pressure
A Multi-Center, Placebo-Controlled Randomized Pilot of the Effect of Sorafenib on Portal Pressure in Patients With Cirrhosis, Portal Hypertension and Hepatocellular Carcinoma Treated With Ablative Therapy and/or Transarterial Chemoembolization
Sorafenib is approved by the US FDA for the treatment of unresectable (can not operate) liver cancer and for renal cell carcinoma. Sorafenib is a drug that inhibits the growth of cancer cells and prevents the formation of new blood vessels that would otherwise help the cancer spread.
Studies in experimental animals have shown that sorafenib may also lower portal vein pressure (the pressure of the blood passing from the intestine through the liver.) This study seeks to determine if sorafenib lowers the blood pressure in liver blood vessels (portal vein pressure) in patients with cirrhosis who have high portal vein pressure. The study will also obtain information whether sorafenib is safe in this patient population.
Half of the patients will be given sorafenib and half will be given a placebo (a pill without any medicine in it.) This allows a comparison of the reactions of people who take sorafenib to those who do not.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
This is a pilot proof-of-concept study that investigates the effect of sorafenib on portal pressure, as determined by the hepatic venous pressure gradient (HVPG), in patients with liver cirrhosis, portal hypertension and unresectable hepatocellular carcinoma (HCC) that has successfully responded to radiofrequency ablation and/or transarterial chemoembolization, and have obtained a complete response.
The primary end-point of the study is the change in HVPG observed from baseline to three months after starting treatment with sorafenib. Secondary end-point is safety of sorafenib.
The trial is structured as a randomized double blind placebo controlled study. After a three-month period of therapy with sorafenib or placebo (double-blind phase), patients will be given open-label sorafenib for an additional 3-month period (open-label phase). A total of 44 patients will be randomized (in the initial phase) on a 1:1 ratio to sorafenib or placebo. Patients will be followed monthly and HCC follow-up will be according to standards of care. The study will be sponsored by Onyx, who will also provide the treatment medication (sorafenib and placebo)
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06520
- Yale Cancer Center
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West Haven, Connecticut, Estados Unidos, 06516
- VA Medical Center West Haven
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham & Womens
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New York
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New York, New York, Estados Unidos, 10016
- New York University Langone Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- University of Pennsylvania School of medicine
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Texas
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Houston, Texas, Estados Unidos, 77030
- The University of Texas Health Science Center at Houston
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
- Age 20-75 years
- Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver, splenomegaly and/or collaterals
- HCC proven histologically or diagnosed following the AASLD criteria if biopsy not feasible or refused by the patient
- HCC must be unresectable and within UCSF criteria (single tumor ≤ 6.5 cm diameter, or, if multiple lesions, maximum diameter of the largest lesion ≤ 4.5 and total tumor diameter ≤ 8 cm (23))
- CPT score <9 (that is all Child A and Child B with a score of 7 or 8)
- Complete response to treatment with RFA (including that performed laparoscopically) or TACE or a combination of the above as defined by radiologic criteria (hepatoma protocol MRI or CT scan performed 4-6 weeks after the procedure).
- No more than two ablative procedures prior to enrollment
- Presence of portal hypertension, as defined by HVPG of >5 mmHg
- EGD for variceal screening performed within 6 months of entry into the study unless the patient is already on a stable dose of a non selective beta-blocker (adjusted to obtain a heart rate of 55-60 bpm) or treated with variceal band ligation.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
- Signed informed consent
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador de Placebo: Placebo
Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
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Comparador de Placebo: Placebo
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Experimental: Sorafenib
Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
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Sorafenibe, 400 mg duas vezes ao dia
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Patients With Change in HVPG From Baseline
Prazo: Three Months
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Number of participants with a decrease in HPVG that was > 10% of baseline
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Three Months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Guadalupe Garcia-Tsao, MD, Yale University
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 1002006266
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