Carcinoma, HepatocellularPhase 2NCT00508001
Phase II Study of Best Support Care (BSC) Plus ZD6474(Vandetanib) in Patients With Inoperable Hepatocellular Carcinoma (HCC)
A Phase 2 study testing Vandetanib in people with Carcinoma, Hepatocellular, run by Genzyme, a Sanofi Company at 3 sites in Taiwan.
Trial summary
This is a multi-centre, phase II study to assess the efficacy and safety of ZD6474 in patients with Child-Pugh class A, inoperable HCC. This study comprises 2 phases, the primary treatment phase and the secondary treatment phase. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Vandetanib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 3 sitesTaiwan
- Study dates
- Jul 2007to Jun 2009
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand and provide informed consent
- Histologically diagnosed HCC, OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis. A clinically diagnosed HCC should fulfil ALL the criteria below.
- Chronic hepatitis B or C and/or evidence of liver cirrhosis
- Presence of hepatic tumour(s) with image findings (sonography, CT scan, or MRI scan) compatible with HCC, and no evidence of other gastrointestinal tumours
- A persistent elevation of serum a-fetoprotein level >= 400 ng/ml without any evidence of an existing a-fetoprotein-secreting germ cell tumour
- Locally advanced (for example, portal vein invasion, multiple nodules, or nodules in both lobes) or metastatic HCC with at least one measurable lesion by RECIST criteria that meets ANY the criteria below:
Show all 18Show fewer
- HCC not suitable to receive local therapy, including surgical resection, percutaneous ethanol injection (PEI), or transarterial chemo-embolization (TACE)
- Disease recurred or was refractory to previous local therapy
- Patients refused local therapy
- At least one measurable lesion by RECIST criteria. Tumour lesions treated previously with local radiotherapy, percutaneous ethanol injection, radiofrequency ablation, or transarterial embolization are NOT considered measurable.
- If they completed percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy at least 4 weeks prior to enrollment, patients must have subsequent progression or recurrence with at least one new measurable lesion that has not been treated with any local procedure.
- Karnofsky performance status >= 70
- Life expectancy >= 2 months
- Child-Pugh class A liver function
- Adequate bone marrow reserve, defined as white blood cell count >= 3,000/ml, and platelet count >= 75,000/ml
- Liver transaminases (AST and ALT) <= 5 times upper normal limits (UNLs); serum bilirubin <= 1.5 times UNL <= 2 mg/dL
- Serum creatinine <= 1.5 times UNL
- Negative pregnancy test for women of childbearing potential. Patients of childbearing age as well as his/her partner must use effective contraception during the study period unless they are surgically sterile or one year post-menopausal
Who cannot join
- Receiving concurrent anti-cancer therapy for HCC, which includes local therapy, chemotherapy, or other experimental therapy
- Prior systemic cytotoxic chemotherapy
- Prior transarterial chemo-embolization (TACE) or hepatic arterial infusion (HAI), with any of the following conditions for those patients who have any target lesions in the liver:
- More than 5 TACE or HAI sessions undergone prior to enrollment
- The cumulative doses of doxorubicin > 120 mg/m2, mitomycin-C > 24 mg/m2, cisplatin > 120 mg/m2, or 5-fluorouracil > 2400 mg/m2
- Details of the TACE or HAI regimens are not available in the chart
Show all 38Show fewer
- (Note: The number of sessions of prior TACE or HAI will not be limited for patients who have no target lesion in the liver).
- Local treatment including radiotherapy (except palliative radiotherapy), percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy completed within 4 weeks prior to enrollment
- Prior therapy targeting VEGF or EGF signalling pathways, including but not limited to bevacizumab, cetuximab, gefitinib, erlotinib, or sorafenib.
- Prior thalidomide therapy is not allowed but for patients who stop thalidomide due to intolerability and meet either one of following condition can be included:
- Patients who took thalidomide for no more than <= 3 days before enrolment
- Patients who took thalidomide for > 3 days but <= 14 days and are confirmed clinically not responding to thalidomide. 14 days washout period is needed before enrolment.
- Laboratory results:
- Serum potassium less than 4.0 mmol/L despite supplementation
- Serum calcium (ionized or adjusted for albumin) or magnesium out of their normal ranges despite supplementation
- Esophagogastroduodenoscopy reveals lesions that are considered high risk of gastrointestinal bleeding
- Brain or leptomeningeal metastases
- History of HCC tumour rupture
- History of upper gastrointestinal bleeding within 1 year
- Current or recent (within 10 days prior to enrollment) users of full-dose oral or parenteral anti-coagulants
- Surgical procedures, open biopsy, or significant traumatic injury within 28 days prior to enrollment. Fine-needle aspiration, core biopsy, and central venous line placement must be done at least 7 days prior to enrollment. Incompletely healed surgical incision prior to enrollment.
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol.
- Clinically significant cardiac event such as myocardial infarction; New York Heart Association classification of heart disease > 2 within 3 months before entry; or other cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
- History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic, requires treatment (CTCAE grade 3), or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, if controlled on medication, will not be excluded.
- Previous history of QTc prolongation as a result of therapy with other medication that required discontinuation of that medication.
- Congenital long QT syndrome, or first-degree relative with unexplained sudden death under 40 years of age
- Presence of left bundle branch block
- QTc with Bazett's correction that is unmeasurable, or >= 480 msec on screening ECG
- Use of any concomitant medication that are generally accepted by authorities to have a risk of causing Torsades de Pointes within 2 weeks before enrollment (use of the concomitant medication that may be associated with Torsades de Pointes but lack substantial evidence of causing Torsades de Pointes is allowed, but the screening QTc must be less then 460 msec, and an additional ECG is required within the first 24 hours after the first dose of study medication is required).
- Use of any concomitant medication that induce CYP3A4 activity within 2 weeks before enrollment
- Use of interferon within 3 months before enrollment
- Hypertension not well controlled by medical therapy (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg)
- Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or diarrhea due to intolerability
- Current pregnancy or breast-feeding
- Other previous or current malignancies within the last 5 years, with the exception of adequately treated cervical carcinoma in situ and basal cell or squamous cell carcinoma of the skin
- Receipt of any investigational agents within 30 days prior to commencing protocol treatment
- Any unresolved toxicity greater than CTC grade 2 from previous anti-cancer therapy
- Known hypersensitivity to ZD6474 or any of its excipients
Trial locations and contacts
3 sites in 1 country.
About this study
Official title: A Randomised, Double-blind, Parallel Group, Multi-centre, Phase II Study to Assess the Efficacy and Safety of Best Support Care (BSC) Plus ZD6474(Vandetanib) 300 mg, BSC Plus ZD6474(Vandetanib) 100 mg, and BSC Plus Placebo in Patients With Inoperable Hepatocellular Carcinoma (HCC)
This is a multi-centre, phase II study to assess the efficacy and safety of ZD6474 in patients with Child-Pugh class A, inoperable HCC. This study comprises 2 phases, the primary treatment phase and the secondary treatment phase. The primary treatment phase is a randomised, double-blind, parallel-group phase II study to assess the efficacy and safety of ZD6474 300 mg plus best support care (BSC), ZD6474 100 mg plus BSC, and placebo plus BSC. The secondary treatment phase is an open-label expanded access program of ZD6474. In the primary treatment phase, patients will be randomised in a 1:1:1 ratio to receive ZD6474 300 mg plus BSC, ZD6474 100 mg plus BSC, or placebo plus BSC, respectively. Randomisation will be stratified on the basis of Cancer of the Liver Italian Programme (CLIP) tumour staging (CLIP score 0-2 versus 3-4). The primary treatment will continue until objective disease progression, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, or until patients meet any other withdrawal or discontinuation criteria.The primary endpoint is tumour stabilisation rate, and the secondary endpoints are objective response rate, progression-free survival, and overall survival. The purpose of the secondary treatment phase is to expand the access of ZD6474 so that every patient who is enrolled into this study can have the chance to receive the active medicine.Once an individual patient has progressive disease in the primary treatment phase, the blind will be broken for this patient. If this patient is in the ZD6474 100 mg arm or placebo arm, the patient will be offered the secondary treatment with ZD6474 300 mg per day. If this patient is randomised to the ZD6474 300 mg arm, the study medication will be discontinued unless the patient wishes to remain the treatment, and the patient is to be followed up for survival.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Vandetanib, Best Supportive Care
- Keywords
- Hepatocellular carcinoma, Advanced solid, malignant tumour
- Medical subject headings
- Carcinoma, Hepatocellular, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VandetanibDrug
Also called Zactima, ZD6474
ZD6474 300mg
VandetanibDrug
Also called Zactima, ZD6474
ZD6474 100 mg
Best Supportive CareDrug
Placebo + Best Supportive Care
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Best Supportive Care + Placebo Receives: Drug: Best Supportive Care |
| 2 | Experimental | Best Supportive Care + ZD6474 100 mg Receives: Drug: Vandetanib |
| 3 | Experimental | Best Supportive Care + ZD6474 300 mg Receives: Drug: Vandetanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumour Stabilisation Rate
Tumour stabilisation rate calculated as percentage of patients with best objective tumour response (Complete Response, Partial Response or Stable Disease) for >=16 weeks based on Response Evaluation Criteria in Solid Tumours (RECIST).
Complete Response - Disappearance of all target lesions; Partial Response - >=30% decrease in the sum of longest diameter of target lesions; Progressive Disease - >=20% increase in the sum of longest diameter of target lesions; Stable Disease - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: After 16 weeks of treatment.
Secondary outcomes (3)
Objective Response Rate
Objective Response rate defined as percentage of patients with Complete Response [CR] or Partial Response [PR] based on Response Evaluation Criteria in Solid Tumours (RECIST).
Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions as assessed by Magnetic Resonance Imaging (MRI). Complete response (CR) must have disappearance of all target and non-target lesions as assessed by MRI.
Measured: After 16 weeks of treatment.
Progression-free Survival
Progression-free survival defined as the period from date of randomization(start of treatment) to date of disease progression or death.
Measured: from the date of randomisation to the date of documented disease progression or death for any cause
Overall Survival
Overall survival defined as the time from randomization (start of treatment) until death from any cause.
Measured: assessed up to 360 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2007 (estimated)
- Study startJul 2007
- Primary completionNov 2008
- Study completionJun 2009
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 Carcinoma, HepatocellularStudies 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
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00508001
- Sponsor's protocol ID
- D4200C00072
- Status last verified
- Aug 2016
- First submitted
- 25 Jul 2007
- Last updated
- 10 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Parallel Group, Multi-centre, Phase II Study to Assess the Efficacy and Safety of Best Support Care (BSC) Plus ZD6474(Vandetanib) 300 mg, BSC Plus ZD6474(Vandetanib) 100 mg, and BSC Plus Placebo in Patients With Inoperable Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT00508001
- Acronym / sponsor ID
- D4200C00072
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Hepatocellular carcinoma, Advanced solid, malignant tumour
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 27 Jul 2007 (estimated)
- Results
- Posted 17 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-centre, phase II study to assess the efficacy and safety of ZD6474 in patients with Child-Pugh class A, inoperable HCC. This study comprises 2 phases, the primary treatment phase and the secondary treatment phase. The primary treatment phase is a randomised, double-blind, parallel-group phase II study to assess the efficacy and safety of ZD6474 300 mg plus best support care (BSC), ZD6474 100 mg plus BSC, and placebo plus BSC. The secondary treatment phase is an open-label expanded access program of ZD6474. In the primary treatment phase, patients will be randomised in a 1:1:1 ratio to receive ZD6474 300 mg plus BSC, ZD6474 100 mg plus BSC, or placebo plus BSC, respectively. Randomisation will be stratified on the basis of Cancer of the Liver Italian Programme (CLIP) tumour staging (CLIP score 0-2 versus 3-4). The primary treatment will continue until objective disease progression, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, or until patients meet any other withdrawal or discontinuation criteria.The primary endpoint is tumour stabilisation rate, and the secondary endpoints are objective response rate, progression-free survival, and overall survival. The purpose of the secondary treatment phase is to expand the access of ZD6474 so that every patient who is enrolled into this study can have the chance to receive the active medicine.Once an individual patient has progressive disease in the primary treatment phase, the blind will be broken for this patient. If this patient is in the ZD6474 100 mg arm or placebo arm, the patient will be offered the secondary treatment with ZD6474 300 mg per day. If this patient is randomised to the ZD6474 300 mg arm, the study medication will be discontinued unless the patient wishes to remain the treatment, and the patient is to be followed up for survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Best Supportive CareBest Supportive Care + Placebo |
| 2 | Experimental | Drug: VandetanibBest Supportive Care + ZD6474 100 mg |
| 3 | Experimental | Drug: VandetanibBest Supportive Care + ZD6474 300 mg |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Able to understand and provide informed consent
- Histologically diagnosed HCC, OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis. A clinically diagnosed HCC should fulfil ALL the criteria below.
- Locally advanced (for example, portal vein invasion, multiple nodules, or nodules in both lobes) or metastatic HCC with at least one measurable lesion by RECIST criteria that meets ANY the criteria below:
- At least one measurable lesion by RECIST criteria. Tumour lesions treated previously with local radiotherapy, percutaneous ethanol injection, radiofrequency ablation, or transarterial embolization are NOT considered measurable.
- If they completed percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy at least 4 weeks prior to enrollment, patients must have subsequent progression or recurrence with at least one new measurable lesion that has not been treated with any local procedure.
Key exclusion criteria (38 listed)
- Receiving concurrent anti-cancer therapy for HCC, which includes local therapy, chemotherapy, or other experimental therapy
- Prior systemic cytotoxic chemotherapy
- Prior transarterial chemo-embolization (TACE) or hepatic arterial infusion (HAI), with any of the following conditions for those patients who have any target lesions in the liver:
- (Note: The number of sessions of prior TACE or HAI will not be limited for patients who have no target lesion in the liver).
- Local treatment including radiotherapy (except palliative radiotherapy), percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy completed within 4 weeks prior to enrollment
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 |
|---|---|---|
| VandetanibAlso: Zactima, ZD6474ZD6474 300mg | Drug | 3 |
| VandetanibAlso: Zactima, ZD6474ZD6474 100 mg | Drug | 2 |
| Best Supportive CarePlacebo + Best Supportive Care | Drug | 1 |
Primary outcome
Tumour Stabilisation Rate
Time frame: After 16 weeks of treatment.
Tumour stabilisation rate calculated as percentage of patients with best objective tumour response (Complete Response, Partial Response or Stable Disease) for >=16 weeks based on Response Evaluation Criteria in Solid Tumours (RECIST). Complete Response - Disappearance of all target lesions; Partial Response - >=30% decrease in the sum of longest diameter of target lesions; Progressive Disease - >=20% increase in the sum of longest diameter of target lesions; Stable Disease - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
3 secondary outcomes
Objective Response Rate
Time frame: After 16 weeks of treatment.
Progression-free Survival
Time frame: from the date of randomisation to the date of documented disease progression or death for any cause
Overall Survival
Time frame: assessed up to 360 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2016.
- 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.
Study Director Clinical Sciences & Operations study director
Sanofi
3 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 Vandetanib in people with Carcinoma, Hepatocellular, run by Genzyme, a Sanofi Company at 3 sites in Taiwan.
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 18 inclusion and 38 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: finished, as of the sponsor's last update on 10 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Taiwan. 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?
Yes. Results are posted in the registry (first posted 17 Jul 2012). 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?
Tumour Stabilisation Rate (time frame: After 16 weeks of treatment.). 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 10 Oct 2016.