Liver CancerPhase 2NCT00524316
Sunitinib and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
A Phase 2 study testing doxorubicin hydrochloride, sunitinib malate and laboratory biomarker analysis in people with Liver Cancer, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs, such as doxorubicin, near the tumor. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Liver Cancer
- What is being tested?
- doxorubicin hydrochloride, sunitinib malate and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to May 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically, cytologically, or serologically* confirmed hepatocellular carcinoma meeting the following criteria:
- 1-4 lesions
- Involvement of 1 or both liver lobes NOTE: *Alpha-fetoprotein (AFP) > 500 mcg/L in high-risk patients
- Measurable disease by CT scan or MRI
- Disease does not exceed 50% of the liver parenchyma
- At least 1 lesion ≥ 3 cm in longest diameter
- Tumor burden involves < 50% of the liver
- Refused surgery OR unresectable disease due to any of the following:
- Multifocality
- Advanced cirrhosis
- Comorbid illness
- Candidate for chemoembolization
- No fibrolamellar histology
- No ascites
- No known brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- WBC ≥ 3,000/mm³
- ANC ≥ 1,500/mm³
- Hemoglobin ≥ 8.5 g/dL (transfusion allowed)
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 2 mg/dL
- AST ≤ 5 times upper limit of normal (ULN)
- INR < 1.5
- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min
- No bleeding diathesis or coagulopathy
- No active congestive heart failure
- No uncontrolled angina
- No myocardial infarction within the past 12 months
- No cardiac arrhythmia
- Ejection fraction ≥ 45% (in patients with known coronary artery disease and in patients > 50 years of age)
- Child-Pugh class A or B cirrhosis
- No impedance of hepatopedal blood flow (portal vein thrombosis)
- No thrombosis of the main portal vein
- No encephalopathy
- No biliary obstruction
- No variceal bleed within the past 6 months
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
- No absolute contraindication to doxorubicin, iodinated contrast material, microfibrillar collage hemostat, or dexamethasone
- No other concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Psychiatric illness or social situation that would limit compliance with study requirements
- No other active malignancies within the past year except nonmelanoma skin cancer or carcinoma in situ
- No significant traumatic injury within the past 4 weeks
- No QTc prolongation (i.e., QTc interval ≥ 500 msec) or other significant ECG abnormalities
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after the completion of study treatment
PRIOR CONCURRENT THERAPY:
- Recovered from prior therapy
- Prior liver-directed therapy, such as chemoembolization, radiofrequency ablation, cryoablation, or ethanol injection allowed if the following criteria are met:
- Treated lesion remains inactive by CT scan or MRI and new lesion being embolized is distinct from the previously treated lesion
- Radiographic progression of previously treated lesion requiring re-embolization
- Prior liver resection allowed
- Prior immunotherapy allowed
- No prior antiangiogenesis therapy
- No prior liver transplantation
- Patients awaiting a cadaveric or orthotopic liver transplantation are eligible provided they have end-stage liver disease with a priority score of < 20 points
- More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 4 weeks since prior major surgery or open biopsy
- At least 1 week since prior fine needle biopsy
- No concurrent immunotherapy
- No concurrent radiotherapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)
- Doses of ≤ 1 mg/day are allowed for prophylaxis of thrombosis as long as INR ≤ 1.5
- Both full dose and prophylactic dose low molecular weight heparin allowed as long as PT INR ≤ 1.5
- No anticipated major surgery during and for 3 months after completion of study treatment
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
About this study
Official title: A Phase II Study of SUNITINIB MALATE (Sutent) and Chemoembolization in Patients With Unresectable Hepatocellular Cancer
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs, such as doxorubicin, near the tumor. Giving sunitinib together with chemoembolization may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving sunitinib together with chemoembolization works in treating patients with liver cancer that cannot be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To determine the progression-free survival at 4 months of patients treated with this regimen.
Secondary
- To determine overall survival of these patients.
- To determine if dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to measure decrease in tumor perfusion and vascular permeability as a result of treatment with sunitinib malate in combination with TACE, and if it can be useful in prognosis.
- To examine the safety and tolerability of this regimen.
- To determine if a change in circulating endothelial precursor cell number and total monocyte count on days 3, 8, 10, and 35 of therapy (as compared with levels at baseline) and decrease in soluble vascular endothelial growth factor receptor-2 in serum on days 8 (before TACE), 10, and 35 of therapy (as compared with baseline) correlate with improved response and survival.
- To determine the effect of this therapy on quality of life as measured by the FACT-HEP scale prior to each course of therapy.
OUTLINE: This is a multicenter study.
Patients receive oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses. Patients undergo hepatic artery chemoembolization with doxorubicin hydrochloride on day 8 of course 1 only. Treatment with sunitinib malate repeats every 6 weeks* in the absence of disease progression or unacceptable toxicity.
NOTE: *Course 1 is 7 weeks in duration; all subsequent courses are 6 weeks in duration.
Blood samples are collected at baseline and periodically during study to measure circulating endothelial precursor cell levels, total monocyte count, and soluble vascular endothelial growth factor receptor-2.
Quality of life is assessed by the FACT-HEP scale at baseline, prior to each course of treatment, and then at the completion of treatment.
After completion of study treatment, patients are followed every 6 months.
- Conditions
- Liver Cancer
- Being tested
- doxorubicin hydrochloride, sunitinib malate, laboratory biomarker analysis, hepatic artery embolization, quality-of-life assessment
- Keywords
- adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transarterial chemoembolization
sunitinib malateDrug
Given Orally
laboratory biomarker analysisOther
Correlative Study
hepatic artery embolizationProcedure or surgery
Surgical procedure
quality-of-life assessmentProcedure or surgery
Correlative Study
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses Receives: Drug: doxorubicin hydrochloride; Drug: sunitinib malate; Other: laboratory biomarker analysis; Procedure: hepatic artery embolization; Procedure: quality-of-life assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
median progression free survival in months
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Secondary outcomes (5)
Overall Survival
median survival in months
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Tissue Perfusion, Ktrans, IAUC, and Percent Viable Tumor as Measured by DCE-MRI at Baseline and on Days 8 (Before Transarterial Chemoembolization), 10, and 35
Measured: Baseline, day 8, day 10, day 28 and day 35
Safety and Tolerability
Number of participants with adverse advent.
Please refer to adverse event reporting for more detail.
Measured: Daily while on treatment through study completion, an average of 1 year
Assess the Change in the Quality of Life Among Patients Using the FACTHep (Version 4) for Hepatobiliary Cancers.
We utilized the FACT-HEP TOTAL SCORE (version 4) quality-of-life scale, which is a 45 item scale ranging from 96-178. Higher scores reflect better quality of life.
No subscales were analyzed.
Measured: Baseline and Cycle 2
Tumor Marker Response (AFP)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Baseline, week 7 and every 6 weeks after
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2007 (estimated)
- Study startApr 2007
- Primary completionDec 2010
- Study completionMay 2014
Why it stopped: low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Renuka Iyer, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00524316
- Sponsor's protocol ID
- CDR0000563261
- Other IDs
- RPCI-I-82706
- Status last verified
- Mar 2017
- First submitted
- 31 Aug 2007
- Last updated
- 9 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of SUNITINIB MALATE (Sutent) and Chemoembolization in Patients With Unresectable Hepatocellular Cancer
- ClinicalTrials.gov ID
- NCT00524316
- Acronym / sponsor ID
- CDR0000563261
- Conditions
- Liver Cancer
- Keywords
- adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- Apr 2007
- Primary completion
- Dec 2010 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 3 Sep 2007 (estimated)
- Results
- Posted 4 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs, such as doxorubicin, near the tumor. Giving sunitinib together with chemoembolization may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving sunitinib together with chemoembolization works in treating patients with liver cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To determine the progression-free survival at 4 months of patients treated with this regimen.
Secondary
- To determine overall survival of these patients.
- To determine if dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to measure decrease in tumor perfusion and vascular permeability as a result of treatment with sunitinib malate in combination with TACE, and if it can be useful in prognosis.
- To examine the safety and tolerability of this regimen.
- To determine if a change in circulating endothelial precursor cell number and total monocyte count on days 3, 8, 10, and 35 of therapy (as compared with levels at baseline) and decrease in soluble vascular endothelial growth factor receptor-2 in serum on days 8 (before TACE), 10, and 35 of therapy (as compared with baseline) correlate with improved response and survival.
- To determine the effect of this therapy on quality of life as measured by the FACT-HEP scale prior to each course of therapy.
OUTLINE: This is a multicenter study.
Patients receive oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses. Patients undergo hepatic artery chemoembolization with doxorubicin hydrochloride on day 8 of course 1 only. Treatment with sunitinib malate repeats every 6 weeks* in the absence of disease progression or unacceptable toxicity.
NOTE: *Course 1 is 7 weeks in duration; all subsequent courses are 6 weeks in duration.
Blood samples are collected at baseline and periodically during study to measure circulating endothelial precursor cell levels, total monocyte count, and soluble vascular endothelial growth factor receptor-2.
Quality of life is assessed by the FACT-HEP scale at baseline, prior to each course of treatment, and then at the completion of treatment.
After completion of study treatment, patients are followed every 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: doxorubicin hydrochloride, Drug: sunitinib malate, Other: laboratory biomarker analysis, Procedure: hepatic artery embolization, Procedure: quality-of-life assessmentoral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| doxorubicin hydrochlorideTransarterial chemoembolization | Drug | Sunitinib |
| sunitinib malateGiven Orally | Drug | Sunitinib |
| laboratory biomarker analysisCorrelative Study | Other | Sunitinib |
| hepatic artery embolizationSurgical procedure | Procedure or surgery | Sunitinib |
| quality-of-life assessmentCorrelative Study | Procedure or surgery | Sunitinib |
Primary outcome
Progression-free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
median progression free survival in months
5 secondary outcomes
Overall Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Tissue Perfusion, Ktrans, IAUC, and Percent Viable Tumor as Measured by DCE-MRI at Baseline and on Days 8 (Before Transarterial Chemoembolization), 10, and 35
Time frame: Baseline, day 8, day 10, day 28 and day 35
Safety and Tolerability
Time frame: Daily while on treatment through study completion, an average of 1 year
Assess the Change in the Quality of Life Among Patients Using the FACTHep (Version 4) for Hepatobiliary Cancers.
Time frame: Baseline and Cycle 2
Tumor Marker Response (AFP)
Time frame: Baseline, week 7 and every 6 weeks after
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Renuka Iyer, MD principal investigator
Roswell Park Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing doxorubicin hydrochloride, sunitinib malate and laboratory biomarker analysis in people with Liver Cancer, run by Roswell Park Cancer Institute at 1 site 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?
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: stopped early, as of the sponsor's last update on 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
Yes. Results are posted in the registry (first posted 4 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 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 May 2017.