Sunitinib Drug Levels and Outcomes in Kidney Cancer

Renal Cell Carcinoma Clinical Trial

— CRESTO  

Official title:

Correlating Renal Cell Cancer Treatment Efficacy With Sunitinib Therapeutic Levels and Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01711268
• Other study ID #: HGWH008
• Status: Recruiting
• Phase: Phase 2
• First received: August 2, 2012
• Last updated: May 13, 2014
• Start date: May 2012
• Est. completion date: December 2014

Study information

• Verified date: May 2014
• Source: Western Sydney Local Health District
• Contact: Howard Gurney, MBBS, FRACP
• Phone: +61298455200
• Email: howard.gurney[@]sydney.edu.au
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Locations

Country	Name	City	State
Australia	Crown Princess Mary Cancer Centre, Westmead Hospital	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Western Sydney Local Health District

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to treatment failure (time on sunitinib treatment)	This duration extends from the date the patient starts sunitinib until the date sunitinib is abandoned. The group with sunitinib concentration below the population median are expected to have a median Time to Treatment Failure (TTF) of approximately 8 months, compared with 14 months in those with sunitinib concentration above the population median.	Sunitinib duration (median)	No
Secondary	Toxicity	Pre-specified toxicities (BP, fatigue, diarrhoea, stomatitis, hand-foot syndrome) will be graded every 6 weeks	Every 6 weeks	No
Secondary	Overall survival	Measured from the date of starting sunitinib treatment to the date of death from any cause	2 years	No
Secondary	Progression-free survival	Progression as determined by the clinician according to RECIST 1.1 definitions	2 years	No
Secondary	Time to second line therapy	Date of starting sunitinib treatment to the date further systemic therapy is started	2 years	No