Clinical trial NCT01078311: Drug Monitoring of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Official title: Phase 2 Study of Measurement of Trough Levels of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatocellular Cancer
Keywords: Patients with advanced hepatocellular cancer
Lead sponsor: South West Sydney Local Health District
Sponsor class: OTHER
First posted: 2010-03-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with advanced HCC who are to commence Sorafenib

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.


Eligibility 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

Primary outcomes:
measure: To demonstrate the correlation of trough sorafenib level with overall survival in advanced hepatocellular carcinoma
timeFrame: 4 years
Secondary outcomes:
measure: To correlate trough sorafenib level with progression free survival
timeFrame: 4 years
measure: To correlate trough sorafenib level with response (disease-control vs progressive disease) by RECIST criteria
timeFrame: 4 years
measure: To correlate trough sorafenib level with alpha fetoprotein (AFP) response
timeFrame: 4 years
measure: To correlate trough sorafenib level with side effects (rash and hypertension)
timeFrame: 4 years
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
References: