NCT01029418

Brief 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. The phase 2 study will look at effectiveness and safety of this drug combination

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P50-P75 for phase_1 hepatocellular-carcinoma

Timeline
Completed

Started Nov 2009

Longer than P75 for phase_1 hepatocellular-carcinoma

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2009

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

December 9, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 10, 2009

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2014

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

April 16, 2015

Status Verified

April 1, 2015

Enrollment Period

4.3 years

First QC Date

December 9, 2009

Last Update Submit

April 14, 2015

Conditions

Hepatocellular Carcinoma

Keywords

HCChepatocellular carcinomaliver cancer

Outcome Measures

Primary Outcomes (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.

    12-15months

Secondary Outcomes (1)

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

    2-3 years

Study Arms (1)

AZD6244 and sorafenib

EXPERIMENTAL

AZD6244+ sorafenib

Drug: AZD6244 and sorafenib

Interventions

AZD6244 and sorafenibDRUG

dose escalation of AZD6244; sorafenib 400mg bd

Also known as: AZD6244,, MEK inhibitor,, sorafenib,, Raf kinase inhibitor, nexavar
AZD6244 and sorafenib

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

National University Hospital Singapore

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Related Publications (2)

  • 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.

    PMID: 19910069BACKGROUND

  • 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.

    PMID: 27681866DERIVED

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver Neoplasms

Interventions

AZD 6244SorafenibMEK inhibitor I

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Su Pin Choo

    National Cancer Centre, Singapore

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Consultant

Study Record Dates

First Submitted

December 9, 2009

First Posted

December 10, 2009

Study Start

November 1, 2009

Primary Completion

February 1, 2014

Study Completion

January 1, 2015

Last Updated

April 16, 2015

Record last verified: 2015-04

Locations

SG(2)