Pilot Study of Effect of Sorafenib on Portal Pressure
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Clinically Significant Portal Hypertension |
Drug: Placebo Drug: Sorafenib |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | 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 |
- Change in HVPG from baseline [ Time Frame: Three Months ] [ Designated as safety issue: No ]Change in HVPG three months after initiation of sorafenib.
- Safety [ Time Frame: 12 months per patient ] [ Designated as safety issue: Yes ]Evaluate safety of sorafenib in this patient population during 3 to 6 months period of use and and up to six months after completion of treatment.
| Estimated Enrollment: | 44 |
| Study Start Date: | August 2011 |
| Estimated Study Completion Date: | August 2014 |
| Estimated Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Placebo
Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
|
Drug: Placebo
Placebo Comparator: Placebo
|
|
Experimental: Sorafenib
Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
|
Drug: Sorafenib
Sorafenib, 400 mg twice daily
|
Detailed Description:
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)
Eligibility| Ages Eligible for Study: | 20 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
- 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
Contacts and Locations| United States, Connecticut | |
| Yale Cancer Center | Recruiting |
| New Haven, Connecticut, United States, 06520 | |
| Contact: Guadalupe Garcia-Tsao, MD 203-737-6063 guadalupe.garcia-tsao@yale.edu | |
| Sub-Investigator: Tamar Taddei, MD | |
| Sub-Investigator: Howard S Hochster, MD | |
| Sub-Investigator: Jill Lacy, MD | |
| Sub-Investigator: Stacey Stein, MD | |
| Sub-Investigator: Mario Strazzabosco, MD | |
| Sub-Investigator: Jeffrey Pollak, MD | |
| Principal Investigator: Guadalupe Garcia-Tsao, MD | |
| United States, Texas | |
| The University of Texas Health Science Center at Houston | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Michael Fallon, MD 713-500-6677 michael.b.fallon@uth.tmc.edu | |
| Principal Investigator: Michael B Fallon, MD | |
| Principal Investigator: | Guadalupe Garcia-Tsao, MD | Yale University |
More Information
No publications provided
| Responsible Party: | Guadalupe Garcia-Tsao, Principal Investigator, Yale University |
| ClinicalTrials.gov Identifier: | NCT01714609 History of Changes |
| Other Study ID Numbers: | HIC # 1002006266 |
| Study First Received: | October 23, 2012 |
| Last Updated: | October 23, 2012 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by Yale University:
|
portal hypertension sorafenib |
Additional relevant MeSH terms:
|
Hypertension Hypertension, Portal Carcinoma, Hepatocellular Vascular Diseases Cardiovascular Diseases Liver Diseases Digestive System Diseases Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type |
Neoplasms Liver Neoplasms Digestive System Neoplasms Neoplasms by Site Sorafenib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013