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AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

Information source: National Cancer Centre, Singapore
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hepatocellular Carcinoma

Intervention: AZD6244 and sorafenib (Drug)

Phase: Phase 1/Phase 2

Status: Terminated

Sponsored by: National Cancer Centre, Singapore

Official(s) and/or principal investigator(s):
Su Pin Choo, Principal Investigator, Affiliation: National Cancer Centre, Singapore

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

Clinical Details

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

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

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

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

Eligibility

Minimum age: 21 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Locations and Contacts

National Cancer Centre Singapore, Singapore 169610, Singapore

National University Hospital Singapore, Singapore 119074, Singapore

Additional Information

Related 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.

Starting date: November 2009
Last updated: April 14, 2015

Page last updated: August 23, 2015

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