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Hepatocellular CarcinomaPhase 1/2NCT01029418

AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

A Phase 1/2 study testing AZD6244 and sorafenib in people with Hepatocellular Carcinoma, run by National Cancer Centre, Singapore at 2 sites in Singapore.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This will be a phase I/II clinical trial testing the combination of sorafenib and AZD6244 in advanced hepatocellular carcinoma with Childs A liver cirrhosis. The aim of the phase I portion is to determine appropriate dose of this drug combination. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
AZD6244 and sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesSingapore
Study dates
Nov 2009to Jan 2015
Phase
Phase 1/2
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 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with unresectable BCLC Stage B/C hepatocellular carcinoma that is biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable)
  • Patients without prior systemic treatment ( chemotherapy or molecular targeted therapy) except prior adjuvant therapy, if given more than 6 months ago
  • Patients who had prior local therapy ( TACE; PEI; RFA) more than 4 weeks prior to study entry
  • No radiotherapy within 4 weeks before entry
  • Child-Pugh class A only ( Appendix A)
  • Age 21 years and older
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  • ECOG performance status 0 or 1 ( Appendix A)
  • Life expectancy > 3 months.
  • Patients must have normal organ and marrow function as defined below:
  • Absolute neutrophil count > 1.5 x 109/L;Platelets> 75 x 109/L; Haemoglobin > 9.0g/dl;Total bilirubin < 51umol/L ( 3 mg /dL); AST(SGOT)/ALT(SGPT) < 5 X institutional ULN; Creatinine 1.5 ULN; INR <1.7 or prothrombin time ( PT) <4 seconds above ULN; Left ventricular ejection fraction (LVEF) >50%
  • Measurable disease according to RECIST. A lesion which has previously been locally treated (including TACE or RFA) is eligible as long as there is evidence of disease progression
  • Suitable for oral administration of drug
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Prior systemic therapy including sorafenib or a MEK inhibitor or sunitinib or other investigational drugs
  • Any prior local therapy ( surgery, radiation therapy, hepatic arterial embolization, or cryoablation) within 4 weeks of study entry.
  • Prior liver transplant
  • NCI CTCAE grade > 3 hemorrhage within 4 weeks of starting study treatment, or documented variceal hemorrhage of any grade within 12 months of study entry (as documented on endoscopy)
  • Presence of esophageal varices (> Grade 2) at risk of bleeding and/or serious or non-healing wound/ulcer ( as documented by endoscopy)
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study entry
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  • Patients with underlying inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea
  • Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism.
  • History of cardiac disease:
  • active congestive heart failure
  • cardiac arrythmias of NCI CTCAE grade >2 or requiring pacemaker
  • uncontrolled hypertension
  • cardiomyopathy
  • atrial fibrillation rate >100bpm
  • Patients with factors that increase the risk of QT prolongation or arrhythmic events ( hypokalemia, family history of long QT interval syndrome) or QTc interval of > 450ms for males or > 470ms for females on screening

Trial locations and contacts

2 sites in 1 country.

Singapore2 sites

  • National University Hospital Singapore

    Singapore, 119074

  • National Cancer Centre Singapore

    Singapore, 169610

Other trials in Singapore

About this study

Official title: A Phase 1/2 Study of AZD6244 in Combination With Sorafenib in Advanced Hepatocellular Carcinoma

This will be a phase I/II clinical trial testing the combination of sorafenib and AZD6244 in advanced hepatocellular carcinoma with Childs A liver cirrhosis. The aim of the phase I portion is to determine appropriate dose of this drug combination. The phase 2 study will look at effectiveness and safety of this drug combination

Read the detailed description

Patients with unresectable BCLC Stage B/C hepatocellular carcinoma that is biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable Patients without prior systemic treatment ( chemotherapy or molecular targeted therapy) except prior adjuvant therapy, if given more than 6 months ago Child-Pugh class A only ECOG performance status 0 or 1

Being tested
AZD6244 and sorafenib
Keywords
HCC, hepatocellular carcinoma, liver cancer
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD6244 and sorafenibDrug

    Also called AZD6244,, MEK inhibitor,, sorafenib,, Raf kinase inhibitor

    dose escalation of AZD6244; sorafenib 400mg bd

Study groups in NCT01029418
Study groupRoleWhat they receive
AZD6244 and sorafenibExperimentalAZD6244+ sorafenib
Receives: Drug: AZD6244 and sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of AZD6244 and sorafenib in patients with advanced hepatocellular cancer.

    Measured: 12-15months

Secondary outcomes (1)

  1. To investigate if the combination sorafenib and AZD6244 increases Time To Progression (TTP) over sorafenib alone in patients with advanced hepatocellular carcinoma patients.

    Measured: 2-3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionFeb 2014
  4. Study completionJan 2015

Why it stopped: The phase II portion was not conducted due to funding issue.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01029418
Sponsor's protocol ID
09-20-HEP
Status last verified
Apr 2015
First submitted
9 Dec 2009
Last updated
16 Apr 2015
Results posted
No
Data monitoring committee
No

Publications

  • Huynh H, Ngo VC, Koong HN, Poon D, Choo SP, Toh HC, Thng CH, Chow P, Ong HS, Chung A, Goh BC, Smith PD, Soo KC. AZD6244 enhances the anti-tumor activity of sorafenib in ectopic and orthotopic models of human hepatocellular carcinoma (HCC). J Hepatol. 2010 Jan;52(1):79-87. doi: 10.1016/j.jhep.2009.10.008. Epub 2009 Oct 28.

    PubMed 19910069

  • Tai WM, Yong WP, Lim C, Low LS, Tham CK, Koh TS, Ng QS, Wang WW, Wang LZ, Hartano S, Thng CH, Huynh H, Lim KT, Toh HC, Goh BC, Choo SP. A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC). Ann Oncol. 2016 Dec;27(12):2210-2215. doi: 10.1093/annonc/mdw415. Epub 2016 Sep 28.

    PubMed 27681866

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD6244 and sorafenib in people with Hepatocellular Carcinoma, run by National Cancer Centre, Singapore at 2 sites in Singapore.

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 13 inclusion and 15 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: stopped early, as of the sponsor's last update on 16 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Singapore. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was stopped early (reason given: The phase II portion was not conducted due to funding issue.). 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?

To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of AZD6244 and sorafenib in patients with advanced hepatocellular cancer. (time frame: 12-15months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01029418, which also lists 2 linked publications.

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 16 Apr 2015.

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