The Effect of Sorafenib on Portal Pressure
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
Primary Outcome Measures
- Patients With Change in HVPG From Baseline [Three Months]
Number of participants with a decrease in HPVG that was > 10% of baseline
Eligibility Criteria
Criteria
-
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale Cancer Center | New Haven | Connecticut | United States | 06520 |
| 2 | VA Medical Center West Haven | West Haven | Connecticut | United States | 06516 |
| 3 | Brigham & Womens | Boston | Massachusetts | United States | 02115 |
| 4 | New York University Langone Medical Center | New York | New York | United States | 10016 |
| 5 | University of Pennsylvania School of Medicine | Philadelphia | Pennsylvania | United States | 19104 |
| 6 | The University of Texas Health Science Center at Houston | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Yale University
- Onyx Therapeutics, Inc.
Investigators
- Principal Investigator: Guadalupe Garcia-Tsao, MD, Yale University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1002006266
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Sorafenib |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo will take two tablets of placebo by mouth twice daily. Placebo: Placebo Comparator: Placebo | Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily. Sorafenib: Sorafenib, 400 mg twice daily |
| Period Title: Overall Study | ||
| STARTED | 5 | 5 |
| COMPLETED | 4 | 5 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo | Sorafenib | Total |
|---|---|---|---|
| Arm/Group Description | Subjects randomized to placebo will take two tablets of placebo by mouth twice daily. Placebo: Placebo Comparator: Placebo | Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily. Sorafenib: Sorafenib, 400 mg twice daily | Total of all reporting groups |
| Overall Participants | 4 | 5 | 9 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
55.98
(4.7)
|
58.78
(4.25)
|
57.38
(4.48)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
4
100%
|
5
100%
|
9
100%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
4
100%
|
5
100%
|
9
100%
|
Outcome Measures
| Title | Patients With Change in HVPG From Baseline |
|---|---|
| Description | Number of participants with a decrease in HPVG that was > 10% of baseline |
| Time Frame | Three Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Sorafenib |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo will take two tablets of placebo by mouth twice daily. Placebo: Placebo Comparator: Placebo | Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily. Sorafenib: Sorafenib, 400 mg twice daily |
| Measure Participants | 4 | 5 |
| Number [participants] |
1
25%
|
1
20%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were collected at the organ class level, unless specified | |||
| Arm/Group Title | Placebo | Sorafenib | ||
| Arm/Group Description | Subjects randomized to placebo will take two tablets of placebo by mouth twice daily. Placebo: Placebo Comparator: Placebo | Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily. Sorafenib: Sorafenib, 400 mg twice daily | ||
All Cause Mortality |
||||
| Placebo | Sorafenib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Sorafenib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/5 (20%) | 0/5 (0%) | ||
| General disorders | ||||
| Fever | 1/5 (20%) | 0/5 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Sorafenib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 5/5 (100%) | ||
| Ear and labyrinth disorders | ||||
| Ear and labyrinth disorders | 1/5 (20%) | 0/5 (0%) | ||
| Gastrointestinal disorders | ||||
| gastrointestinal disorders | 5/5 (100%) | 5/5 (100%) | ||
| General disorders | ||||
| General Disorders | 4/5 (80%) | 4/5 (80%) | ||
| INR increased | 1/5 (20%) | 0/5 (0%) | ||
| Platelet Count Decrease | 1/5 (20%) | 0/5 (0%) | ||
| Hepatobiliary disorders | ||||
| Alanine aminostranferase | 1/5 (20%) | 0/5 (0%) | ||
| Blood Bilirubin Increase | 1/5 (20%) | 0/5 (0%) | ||
| Infections and infestations | ||||
| Infections and infestations | 1/5 (20%) | 1/5 (20%) | ||
| Metabolism and nutrition disorders | ||||
| Metabolism and nutrition disorders | 3/5 (60%) | 2/5 (40%) | ||
| Weight Loss | 1/5 (20%) | 1/5 (20%) | ||
| Weight Gain | 0/5 (0%) | 1/5 (20%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muskoloskeletal and connective tissue | 2/5 (40%) | 1/5 (20%) | ||
| Nervous system disorders | ||||
| Nervous System Disorders | 3/5 (60%) | 4/5 (80%) | ||
| Psychiatric disorders | ||||
| Psychiatric disorders | 2/5 (40%) | 1/5 (20%) | ||
| Reproductive system and breast disorders | ||||
| Reproductive system and breast disorders | 1/5 (20%) | 0/5 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Respitory, thoracic and medistinal | 2/5 (40%) | 2/5 (40%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Skin and subcutaneous tissue disorders | 4/5 (80%) | 5/5 (100%) | ||
| Vascular disorders | ||||
| Vascular disorders | 2/5 (40%) | 0/5 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Garcia-Tsao |
|---|---|
| Organization | Yale University |
| Phone | (203) 737-6063 |
| guadalupe.garcia-tsao@yale.edu |
- 1002006266