Drug Monitoring of Sorafenib in Patients With Advanced Hepatocellular Carcinoma (DOSE-HEP)

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief 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.

Condition or disease
Hepatocellular Cancer

Study Design

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Study Type :	Observational
Estimated Enrollment :	100 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Phase 2 Study of Measurement of Trough Levels of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Study Start Date :	February 2010
Estimated Primary Completion Date :	February 2012
Estimated Study Completion Date :	February 2014

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
HCC patients on Sorafenib

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. To demonstrate the correlation of trough sorafenib level with overall survival in advanced hepatocellular carcinoma [ Time Frame: 4 years ]

Secondary Outcome Measures :

1. To correlate trough sorafenib level with progression free survival [ Time Frame: 4 years ]
2. To correlate trough sorafenib level with response (disease-control vs progressive disease) by RECIST criteria [ Time Frame: 4 years ]
3. To correlate trough sorafenib level with alpha fetoprotein (AFP) response [ Time Frame: 4 years ]
4. To correlate trough sorafenib level with side effects (rash and hypertension) [ Time Frame: 4 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Patients with advanced HCC who are to commence Sorafenib

Criteria

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

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Mark Wong, MBBS, FRACP	61298455200 ext 55200	Mark.Wong@swahs.health.nsw.gov.au

Locations

Australia, New South Wales
Westmead Hospital	Recruiting
Westmead, New South Wales, Australia, 2145

Sponsors and Collaborators

South West Sydney Local Health District

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Mark Wong, Westmead Medical Oncology
ClinicalTrials.gov Identifier:	NCT01078311 History of Changes
Other Study ID Numbers:	MWWH009
First Posted:	March 2, 2010
Last Update Posted:	March 2, 2010
Last Verified:	February 2010

Keywords provided by South West Sydney Local Health District:

Patients with advanced hepatocellular cancer

Additional relevant MeSH terms:

Carcinoma, Hepatocellular; Liver Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms	Neoplasms by Site; Digestive System Diseases; Liver Diseases; Sorafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action