HCV-RNA Kinetics During Sorafenib for Hepatocellular Carcinoma (HCC)

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01849588
• Collaborator: (none)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Duration (Months): 44.1
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This research study is a Phase IV clinical trial. Phase IV trials are used to further test and monitor the safety of a drug approved by the FDA and to see if the drug has any other indications that can be used to treat different diseases.

Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of liver cancer. It is also currently being tested in various other cancers. Sorafenib works by slowing down and/or stopping the development of new cancer cells and new blood vessels. By slowing down and/or stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents or slows down the growth of tumors.

The researchers of this study would like to study the effects of sorafenib on hepatitis C by drawing additional research blood samples from people infected with hepatitis C who are receiving sorafenib treatment for liver cancer. These tests will measure certain proteins in the blood (HCV-RNA) which may indicate if sorafenib has any effect on the hepatitis C virus.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Cancer	Drug: Sorafenib	Phase 4

Detailed Description

This is a prospective, open-label, non-interventional trial to evaluate HCV-RNA levels during treatment with Sorafenib in patients with advanced hepatocellular carcinoma.

Participants will receive Sorafenib 400mg orally twice daily. HCV-RNA (Hepatitis C Virus - Ribonucleic Acid) levels will be measured at baseline, week 2 of sorafenib, week 4 of sorafenib, week 6 of sorafenib, week 8 of sorafenib, week 12 of sorafenib, and 2 weeks after discontinuing sorafenib. HCV-RNA levels will be measured by drawing about 2 tablespoons of blood

During the study period, tumor assessments will be done by MRI (magnetic resonance imaging) or CT (computed tomography) scans at baseline and every 8 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Study of HCV-RNA Kinetics During Treatment With Sorafenib in Patients With Advanced Hepatocellular Carcinoma and Chronic Hepatitis C
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Sorafenib taken orally twice per day	Drug: Sorafenib; Other Names: Nexavar

Outcome Measures

Primary Outcome Measures

1. Decline in HCV-RNA Level [up to 2 years]

   Successful decline in HCV (hepatitis C virus)-RNA level, with success defined as a decrease of at least two logs of HCV-RNA between baseline and any subsequent measurement.

Secondary Outcome Measures

1. Time to Radiological Tumor Progression [2 years]

   Time to radiological tumor progression is defined as the time period between enrollment and the earlier of tumor progression and death. Participants who are alive and progression-free at the date of last contact will be censored at this date.

2. Overall Survival [2 years]

   Overall survival is defined as the time period between enrollment and the date of death. Participants who are still alive at last contact will be censored at this date.

Other Outcome Measures

1. Decrease Alpha-fetoprotein(AFP) Level > 20% From the Baseline [2 years]

   The proportion of participants with a decrease of greater than 20% in AFP (alpha-fetoprotein) level between baseline and any subsequent measurement following treatment with sorafenib will be reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically and/or radiologically confirmed advanced HCC

• Detectable HCV RNA with anti-HCV-positivity

• Life expectancy of at least 3 months

• Willing to use adequate contraception

Exclusion Criteria:

• Pregnant or breastfeeding

• Undetectable HCV RNA

• Uncontrolled hypertension

• Active or clinically significant cardiac disease

• Thrombolic, embolic, venous or arterial events within 6 months of informed consent

• Pulmonary hemorrhage/bleeding event (NCI-CTCAE grade 2 or higher) within 4 weeks before study entry

• Previously untreated or concurrent cancer except cervical cancer in situ, treated basal cell carcinoma or superficial bladder tumor

• Presence of non-healing wound, ulcer or bone fracture

• History of organ allograft

• Known or suspected allergy or hypersensitivity to any of the study drugs

• Any malabsorption condition

• Inability to comply with the protocol and/or not willing or not available for follow up

• Major surgery within 30 days prior to start of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Andrew Zhu, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Andrew X. Zhu, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01849588
• Other Study ID Numbers: 12-213
• First Posted: May 8, 2013
• Last Update Posted: Apr 19, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Andrew X. Zhu, MD, Principal Investigator, Massachusetts General Hospital: Hepatitis C positive
• Additional relevant MeSH terms: Carcinoma, Hepatocellular; Liver Neoplasms; Sorafenib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between December 2013 and December 2015

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
Overall Participants	3
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.8
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	Decline in HCV-RNA Level
Description	Successful decline in HCV (hepatitis C virus)-RNA level, with success defined as a decrease of at least two logs of HCV-RNA between baseline and any subsequent measurement.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
Measure Participants	3
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Time to Radiological Tumor Progression
Description	Time to radiological tumor progression is defined as the time period between enrollment and the earlier of tumor progression and death. Participants who are alive and progression-free at the date of last contact will be censored at this date.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Study was terminated early due to slow accrual.

Arm/Group Title	Treatment Arm
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
Measure Participants	3
Mean (Full Range) [months]	5.68

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time period between enrollment and the date of death. Participants who are still alive at last contact will be censored at this date.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
Measure Participants	3
Mean (Full Range) [months]	8.36

4. Other Pre-specified Outcome

Title	Decrease Alpha-fetoprotein(AFP) Level > 20% From the Baseline
Description	The proportion of participants with a decrease of greater than 20% in AFP (alpha-fetoprotein) level between baseline and any subsequent measurement following treatment with sorafenib will be reported.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

AFP levels were not available for one participant.

Arm/Group Title	Treatment Arm
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
Measure Participants	2
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Participants are monitored for adverse events throughout their entire time on study. This was a maximum of 13 months.
Adverse Event Reporting Description	Only events possibly, probably, or definitely related to administration of sorafenib are listed here.
Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib taken orally twice per day Sorafenib
All Cause Mortality
	Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
anemia	2/3 (66.7%)
Gastrointestinal disorders
diarrhea	3/3 (100%)
nausea	2/3 (66.7%)
GI bleed	1/3 (33.3%)
vomiting	1/3 (33.3%)
abdominal pain	1/3 (33.3%)
bloating	2/3 (66.7%)
ascites	1/3 (33.3%)
dyspepsia	1/3 (33.3%)
periodontal disease	1/3 (33.3%)
General disorders
fatigue	2/3 (66.7%)
chills	1/3 (33.3%)
non-cardiac chest pain	1/3 (33.3%)
Investigations
platelet count decreased	3/3 (100%)
elevated bilirubin	3/3 (100%)
elevated alkaline phosphatase	3/3 (100%)
weight loss	1/3 (33.3%)
SGOT increased	3/3 (100%)
SGPT increased	2/3 (66.7%)
Metabolism and nutrition disorders
anorexia	1/3 (33.3%)
low phosphorus	3/3 (100%)
hyperglycemia	2/3 (66.7%)
hyperkalemia	1/3 (33.3%)
hypoalbuminemia	1/3 (33.3%)
hypocalcemia	1/3 (33.3%)
hypoglycemia	1/3 (33.3%)
hypomagnesemia	1/3 (33.3%)
hyponatremia	1/3 (33.3%)
Nervous system disorders
headache	1/3 (33.3%)
Psychiatric disorders
anxiety	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
epistaxis	1/3 (33.3%)
Hoarseness	1/3 (33.3%)
Skin and subcutaneous tissue disorders
palmar-plantar erythrodysesthesia	2/3 (66.7%)
erythema	1/3 (33.3%)
facial rash	1/3 (33.3%)
pruritis	1/3 (33.3%)
Vascular disorders
hypertension	1/3 (33.3%)

Limitations/Caveats

Study was terminated early due to slow accrual, therefore a small number of participants were analyzed and the data are not statistically significant.

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.