Clinical trial NCT01711268: Sunitinib Drug Levels and Outcomes in Kidney Cancer
Official title: Correlating Renal Cell Cancer Treatment Efficacy With Sunitinib Therapeutic Levels and Outcomes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Renal Cell Carcinoma
Keywords: Sunitinib
Renal Cell Carcinoma
Therapeutic Drug Monitoring
Pharmacokinetic
Treatment toxicity
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
First posted: 2012-10-22
Enrollment: 35
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: Adults being treated with sunitinib monotherapy for metastatic renal cell carcinoma

Brief summary: Sunitinib is an oral drug used for treatment of advanced kidney cancer. The standard dose is 50mg, but many patients require a dose decrease due to side-effects. Drug levels of sunitinib vary approximately 10-fold between patients.

This study will measure blood levels of sunitinib and its metabolite, and correlate these with side-effects and the response to the treatment. The study aims to establish whether blood levels change with time, and see how useful blood levels are for monitoring patients treated with sunitinib.

Detailed description: Rationale: Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used for first-line systemic therapy in metastatic renal cell carcinoma. It is metabolised to a pharmacologically active metabolite, SU012662, which is of equal potency to the parent compound. At a standard 50mg daily dose, variability in plasma levels between patients is approximately ten-fold. In clinical trials, over 30% of patients require a dose reduction due to toxicity. However, some patients can tolerate up to 100mg without excessive toxicity. It is unknown if sunitinib clearance changes with time. Pre-clinical experiments observed tyrosine kinase inhibition at a plasma concentration of 50-100ng/ml.

Design: This is a prospective non-randomized, Phase II clinical study. Decision to treat patients with single-agent sunitinib is pre-determined by treating specialists before entering this study. Toxicity and trough sunitinib/metabolite levels will be measured every six weeks during treatment.

Aim: This study will prospectively examine the relationship between steady-state trough levels of sunitinib/metabolites and the time on treatment, in addition to changes in trough levels over time. Trough levels will also be correlated with other measures of efficacy and treatment-related toxicity. Furthermore, we aim to confirm that the putative target of 50ng/ml correlates with toxicity and time on sunitinib.

Eligibility criteria: Inclusion Criteria:

* Metastatic renal cell cancer treated with single agent sunitinib
* No known primary liver disease and no other severe or uncontrolled concurrent medical conditions
* Signed informed consent

Exclusion Criteria:

* Patients who are unable to sign informed consent
* Patients unable to give blood
* Patients who are pregnant, nursing or not using an effective contraception method
* Patients who had bone-marrow-transplantation prior to sunitinib treatment

Primary outcomes:
measure: Time to treatment failure (time on sunitinib treatment)
timeFrame: Sunitinib duration (median)
Secondary outcomes:
measure: Toxicity
timeFrame: Every 6 weeks
measure: Overall survival
timeFrame: 2 years
measure: Progression-free survival
timeFrame: 2 years
measure: Time to second line therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Crown Princess Mary Cancer Centre, Westmead Hospital
state: New South Wales
Study officials:
affiliation: Crown Princess Mary Cancer Centre, Westmead
name: Howard Gurney, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
References: