HCCPhase 2NCT01265576
Study of Sorafenib With or Without VT-122 in Patients With Hepatocellular Carcinoma (HCC)
A Phase 2 study testing Sorafenib and VT-122 (propranolol plus etodolac) in people with HCC, run by Vicus Therapeutics at 10 sites in United States.
Trial summary
The purpose of this study is to determine if VT-122 provides a clinical benefit when added to Sorafenib in patients with advanced hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCC
- What is being tested?
- Sorafenib and VT-122 (propranolol plus etodolac)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 10 sitesUnited States
- Study dates
- Dec 2010to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants will be required to meet all of the following criteria to be considered eligible for the study:
- Have a confirmed diagnosis of HCC. Biopsy is preferred but is not required.
- Male and female participants who are ≥18 years of age.
- In the opinion of the investigator, the participants have a life expectancy of at least 12 weeks.
- Able to take food or nutritional support orally.
- On sorafenib for at least 4 weeks prior to randomization. Dose adjustments are allowed prior to randomization.
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- Have a Karnofsky Performance Score (KPS) equal to or greater than 50.
- Have a cirrhotic status of Child-Pugh Class A or B7.
- Have the following laboratory parameters:
- a. Platelet count ≥50 x 10E9/L.
- b. Total bilirubin ≤1.5 mg/dL (≤1.0 mg/dL for primary biliary cirrhosis). If total bilirubin >1.5 mg/dL but <3.0 mg/dL, a patient could be enrolled after consultation with the Medical Monitor. If total bilirubin is >3.0 mg/dL, but the value has been constant for a period of greater than 3 months, a patient could be enrolled after consultation with the Medical Monitor.
- c. Serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance >60 mL/min calculated using Cockcroft-Gault.
- d. Serum albumin ≤3.5 g/dL and/or C-reactive protein (CRP) ≥3 mg/L
- Able to provide written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, for any reason without prejudice.
Who cannot join
- Participants must not have any of the following criteria to be considered eligible for inclusion in the study:
- The patient has a history of another primary cancer, with the exception of: a) curatively resected non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor with no known active disease present that in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis.
- Contraindication to sorafenib, propranolol, etodolac, or placebo.
- Patient currently on beta-blockers for the treatment of portal hypertension or arrhythmia. [Patients on beta blockers for the treatment of hypertension are allowed if they change to a different drug class, e.g. some classes of angiotensin-converting enzyme (ACE) inhibitors, for controlling hypertension at least one week before randomization].
- Body mass index (BMI) <17.5 kg/m2.
- History or evidence of cardiac disease: congestive heart failure; New York Heart Association class 2 or greater; active coronary artery disease; unstable angina, cardiac arrhythmias requiring anti-arrhythmic therapy, atrioventricular block of second or third degree, or uncontrolled hypertension. Patients with recent (less than 6 months) myocardial infarction (MI) or coronary revascularization.
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- Hypotension at the time of screening (i.e., systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg).
- Resting heart rate <60 bpm at time of screening.
- Participants with a recent diagnosis of bleeding varices that has not been resolved for a minimum period of 4 weeks.
- Any uncontrolled intercurrent illness that, in the opinion of the Investigator, may interfere with study evaluation.
- On chronotropic drugs (acetylcholine, digoxin, diltiazem, verapamil, atropine, dopamine, dobutamine, epinephrine, isoproterenol).
- Active clinically serious infections [>Grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0].
- Known history of human immunodeficiency virus (HIV) infection.
- Known central nervous system tumors including metastatic brain disease.
- Clinically significant gastrointestinal (GI) bleeding within 30 days prior to Screening.
- Substance abuse, medical, psychological or social conditions that may, in the in the opinion of the investigator, interfere with the patient's participation in the study or evaluation of the study results.
- Known or suspected allergy to the investigational agents or any agent given in association with this trial (hypersensitivity reaction, hives, rash, difficulty breathing swelling of face, lips, tongue, or throat).
- Inability to swallow oral medications.
- Any condition that is unstable or which in the opinion of the Investigator could jeopardize the safety of the patient and his/her compliance in the study.
- Pregnant or breastfeeding participants. Women of childbearing potential (non-childbearing potential is defined as menopausal for at least 2 years, post-bilateral tubal ligation for at least 1 year, post-bilateral oophorectomy or post-hysterectomy) must have a negative urine pregnancy test performed within 10 days prior to the start of study drug. Both men and women enrolled in this trial must use adequate double-barrier birth control measures [2 types of an acceptable form of FDA-approved contraception (e.g., barrier method, Depo-Provera™, Norplant™, Ortho Evra® [birth control patch], oral contraceptives)] during the course of the trial.
- Participation in any other investigational trial in which receipt of investigational drug or device occurred within 30 days prior to screening for this study.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Vicus Clinical Site
Atlanta, Georgia, 30318
Vicus Clinical Site
Berkeley, California, 94704
Vicus Clinical Site
Buffalo, New York, 14263
Vicus Clinical Site
Houston, Texas, 77024
Vicus Clinical Site
Houston, Texas, 77030
Vicus Clinical Site
New Brunswick, New Jersey
Vicus Clinical Site
New York, New York, 10016
Vicus Clinical Site
Newark, New Jersey, 07103
Vicus Clinical Site
Paterson, New Jersey, 07503
Vicus Clinical Site
Philadelphia, Pennsylvania
About this study
Official title: A Randomized, Double Blind, Placebo Controlled, Multicenter Phase 2 Study of VT-122 in Combination With Sorafenib Compared to Sorafenib With Placebo in Patients With Hepatocellular Carcinoma and Systemic Inflammation at Risk for Cachexia
The purpose of this study is to determine if VT-122 provides a clinical benefit when added to Sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Read the detailed description
The most common clinical course of the patient with cancer is local tumor progression leading to the development of metastases, systemic inflammation and the ensuing symptom cluster known as anorexia-cachexia syndrome. This syndrome includes cachexia (anorexia, weight loss and muscle wasting), fatigue, weakness, pain, dyspnea, nausea, malaise, depression and poor performance status. Patients suffering from this syndrome also have poor tolerance, adherence and response to anti-cancer therapy, resulting in disease progression and reduced life expectancy. In spite of the dire need, no proven options for treating inflammatory cancer cachexia are currently available.
VT-122 is the co-administration of the cyclo-oxygenase 2 (COX-2) inhibitor, etodolac and the beta-adrenergic antagonist, propranolol.
It is proposed that these drugs can attenuate systemic inflammation and ameliorate the symptoms of inflammatory cachexia in patients with advanced cancer. As a result, this treatment may improve tolerability and adherence to anti-cancer therapy, thereby yielding direct and indirect benefits in reducing disease progression and improving both the life expectancy and quality of life for patients with advanced cancer.
The potentially synergistic activities of beta blockers and COX-2 inhibitors, their offsetting side effects and their known beneficial impact on co-morbidities associated with liver failure may make them well-suited for use with sorafenib, the standard of care for patients with advanced HCC.
The purpose of this study is to assess whether use of VT-122 is safe and effective in cachectic patients with advanced HCC. In addition to assessing cachexia-related symptoms, the ability of the VT-122 regimen to improve tolerability to sorafenib and thereby to improve both survival and quality of life will also be assessed.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Participants will be on sorafenib at least 30 days before randomization into either the Treatment or Control Arms. Sorafenib will be administered according to the package insert unless contraindicated based on physician expertise.
VT-122 (propranolol plus etodolac)Drug
Participants randomized to the VT-122 regimen (sorafenib plus VT-122) will receive oral doses of propranolol and etodolac, which will be titrated over a period of 3 weeks until the participant reaches a maximum tolerated dose (MTD)[no higher than 60 mg propranolol, twice daily (BID)/300 mg etodolac, BID]. Once the individual MTD has been reached, participants will enter a Maintenance Treatment period, and will receive the VT-122 regimen (propranolol and etodolac, co administered orally) on a continuous BID dosing schedule for a maximum of twelve 4-week cycles.
PlaceboDrug
Participants randomized to the Control Arm (sorafenib with placebo) will receive placebo for the same periods as participants randomized to the Treatment Arm. Participants in the Control Arm will undergo the same visits and mock dose escalation.
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib with placebo | Placebo comparator | Participants randomized to the Control Arm (sorafenib with placebo) receive sorafenib as the standard of care, and placebo for the same periods as participants randomized to the Treatment Arm (sorafenib plus VT-122). Participants randomized to the Control Arm will undergo the same visits and procedures as would the participants randomized to the Treatment Arm. Receives: Drug: Sorafenib; Drug: Placebo |
| Sorafenib plus VT-122 | Experimental | Not described Receives: Drug: Sorafenib; Drug: VT-122 (propranolol plus etodolac) |
What is being measured
The primary outcome is the main question the study is designed to answer.
failure free survival
Measured: 6 months
Secondary outcomes (1)
clinical benefit response
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionFeb 2014
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vicus Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265576
- Sponsor's protocol ID
- VT1-CAX-200
- Status last verified
- Dec 2015
- First submitted
- 21 Dec 2010
- Last updated
- 9 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo Controlled, Multicenter Phase 2 Study of VT-122 in Combination With Sorafenib Compared to Sorafenib With Placebo in Patients With Hepatocellular Carcinoma and Systemic Inflammation at Risk for Cachexia
- ClinicalTrials.gov ID
- NCT01265576
- Acronym / sponsor ID
- VT1-CAX-200
- Conditions
- HCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Vicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Feb 2014 (actual)
- Study completion
- Apr 2016 (estimated)
- First posted
- 23 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if VT-122 provides a clinical benefit when added to Sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Detailed description
The most common clinical course of the patient with cancer is local tumor progression leading to the development of metastases, systemic inflammation and the ensuing symptom cluster known as anorexia-cachexia syndrome. This syndrome includes cachexia (anorexia, weight loss and muscle wasting), fatigue, weakness, pain, dyspnea, nausea, malaise, depression and poor performance status. Patients suffering from this syndrome also have poor tolerance, adherence and response to anti-cancer therapy, resulting in disease progression and reduced life expectancy. In spite of the dire need, no proven options for treating inflammatory cancer cachexia are currently available.
VT-122 is the co-administration of the cyclo-oxygenase 2 (COX-2) inhibitor, etodolac and the beta-adrenergic antagonist, propranolol.
It is proposed that these drugs can attenuate systemic inflammation and ameliorate the symptoms of inflammatory cachexia in patients with advanced cancer. As a result, this treatment may improve tolerability and adherence to anti-cancer therapy, thereby yielding direct and indirect benefits in reducing disease progression and improving both the life expectancy and quality of life for patients with advanced cancer.
The potentially synergistic activities of beta blockers and COX-2 inhibitors, their offsetting side effects and their known beneficial impact on co-morbidities associated with liver failure may make them well-suited for use with sorafenib, the standard of care for patients with advanced HCC.
The purpose of this study is to assess whether use of VT-122 is safe and effective in cachectic patients with advanced HCC. In addition to assessing cachexia-related symptoms, the ability of the VT-122 regimen to improve tolerability to sorafenib and thereby to improve both survival and quality of life will also be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sorafenib with placebo | Placebo comparator | Drug: Sorafenib, Drug: PlaceboParticipants randomized to the Control Arm (sorafenib with placebo) receive sorafenib as the standard of care, and placebo for the same periods as participants randomized to the Treatment Arm (sorafenib plus VT-122). Participants randomized to the Control Arm will undergo the same visits and procedures as would the participants randomized to the Treatment Arm. |
| Sorafenib plus VT-122 | Experimental | Drug: Sorafenib, Drug: VT-122 (propranolol plus etodolac) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Participants will be required to meet all of the following criteria to be considered eligible for the study:
- Have a confirmed diagnosis of HCC. Biopsy is preferred but is not required.
- Male and female participants who are ≥18 years of age.
- In the opinion of the investigator, the participants have a life expectancy of at least 12 weeks.
- Able to take food or nutritional support orally.
Key exclusion criteria (21 listed)
- Participants must not have any of the following criteria to be considered eligible for inclusion in the study:
- The patient has a history of another primary cancer, with the exception of: a) curatively resected non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor with no known active disease present that in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis.
- Contraindication to sorafenib, propranolol, etodolac, or placebo.
- Patient currently on beta-blockers for the treatment of portal hypertension or arrhythmia. [Patients on beta blockers for the treatment of hypertension are allowed if they change to a different drug class, e.g. some classes of angiotensin-converting enzyme (ACE) inhibitors, for controlling hypertension at least one week before randomization].
- Body mass index (BMI) <17.5 kg/m2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibParticipants will be on sorafenib at least 30 days before randomization into either the Treatment or Control Arms. Sorafenib will be administered according to the package insert unless contraindicated based on physician expertise. | Drug | Sorafenib plus VT-122, Sorafenib with placebo |
| VT-122 (propranolol plus etodolac)Participants randomized to the VT-122 regimen (sorafenib plus VT-122) will receive oral doses of propranolol and etodolac, which will be titrated over a period of 3 weeks until the participant reaches a maximum tolerated dose (MTD)[no higher than 60 mg propranolol, twice daily (BID)/300 mg etodolac, BID]. Once the individual MTD has been reached, participants will enter a Maintenance Treatment period, and will receive the VT-122 regimen (propranolol and etodolac, co administered orally) on a continuous BID dosing schedule for a maximum of twelve 4-week cycles. | Drug | Sorafenib plus VT-122 |
| PlaceboParticipants randomized to the Control Arm (sorafenib with placebo) will receive placebo for the same periods as participants randomized to the Treatment Arm. Participants in the Control Arm will undergo the same visits and mock dose escalation. | Drug | Sorafenib with placebo |
Primary outcome
failure free survival
Time frame: 6 months
1 secondary outcome
clinical benefit response
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib and VT-122 (propranolol plus etodolac) in people with HCC, run by Vicus Therapeutics at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
failure free survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2015.