Drug Monitoring of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Hepatocellular Cancer Clinical Trial

— DOSE-HEP  

Official title:

Phase 2 Study of Measurement of Trough Levels of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01078311
• Other study ID #: MWWH009
• Status: Recruiting
• Phase: N/A
• First received: March 1, 2010
• Last updated: March 1, 2010
• Start date: February 2010
• Est. completion date: February 2014

Study information

• Verified date: February 2010
• Source: South West Sydney Local Health District
• Contact: Mark Wong, MBBS, FRACP
• Phone: 61298455200
• Email: Mark.Wong[@]swahs.health.nsw.gov.au
• Is FDA regulated: No
• Health authority: Australia:SWAHS Human Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

Sorafenib improves overall survival and progression free survival in advanced hepatocellular carcinoma. Wide interindividual pharmacokinetic variability was observed. Data from early phase trials in solid tumours showed trough sorafenib levels were associated with incidence of skin rash and hypertension. Rash, hypertension and higher trough levels were moderately predictive of progression free survival.The trough level of sorafenib may be predictive of survival and response in patients treated with sorafenib for advanced hepatocellular carcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 2014
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ECOG = 2

• Histologically or cytologically diagnosed hepatocellular carcinoma, or diagnosis on at least one cross-sectional imaging with the characteristic appearance of HCC (i.e. liver lesion with arterial enhancement and portal venous washout)

• Decision to treat with single agent sorafenib at 400mg bid (dose reductions or interruptions are permitted if side effects occur during treatment)

• No prior systemic chemotherapy or targeted therapy

• Child-Pugh liver function class A or B

• At least one untreated target lesion that can be measured in one dimension according to RECIST

• Adequate organ functions

Exclusion Criteria:

• Prior systemic chemotherapy or molecularly targeted therapy

• Concurrent active malignancy

• Concomitant strong CYP3A4 induced or inhibitor at a therapeutic dose (see section 6.4.1)

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent

• Hypertension that cannot be controlled by medications (> 150/100 mmHg despite optimal medical therapy)

• History of, or known brain metastases (skull metastases allowed), carcinomatous meningitis, or leptomenigeal disease

• Major surgery (e.g. open abdominal therapy, pelvic, thoracic, orthopaedic or neurosurgery) within 4 weeks of the date of first dose

• Local-regional treatment (i.e. percutaneous and trans-arterial procedures) within 4 weeks. Restaging CT or MRI scan must be repeated at least 4 weeks after local-regional treatment and within 3 weeks before the date of first dose

• For patients treated with Yttrium (90Y) radiotherapy, a washout period of 2 months is required.

• 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

• Pregnancy or breast feeding

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Cancer
• Liver Neoplasms

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
South West Sydney Local Health District

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate the correlation of trough sorafenib level with overall survival in advanced hepatocellular carcinoma		4 years	No
Secondary	To correlate trough sorafenib level with progression free survival		4 years	No
Secondary	To correlate trough sorafenib level with response (disease-control vs progressive disease) by RECIST criteria		4 years	No
Secondary	To correlate trough sorafenib level with alpha fetoprotein (AFP) response		4 years	No
Secondary	To correlate trough sorafenib level with side effects (rash and hypertension)		4 years	No