Sunitinib Drug Levels and Outcomes in Kidney Cancer (CRESTO)

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

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.

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma

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.

• Study Type: Observational
• Enrollment (Anticipated): 35

Contacts and Locations

• Study Contact: Name: Howard Gurney, MBBS, FRACP; Phone Number: +61298455200; Email: howard.gurney@sydney.edu.au

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Crown Princess Mary Cancer Centre, Westmead Hospital
      • Contact: Howard Gurney, MBBS (Hon), FRACP; Phone Number: +61298455200; Email: howard.gurney@sydney.edu.au
      • Principal Investigator: Howard Gurney, MBBS (Hon), FRACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adults being treated with sunitinib monotherapy for metastatic renal cell carcinoma

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Pre-specified toxicities (BP, fatigue, diarrhoea, stomatitis, hand-foot syndrome) will be graded every 6 weeks	Every 6 weeks
Overall survival	Measured from the date of starting sunitinib treatment to the date of death from any cause	2 years
Progression-free survival	Progression as determined by the clinician according to RECIST 1.1 definitions	2 years
Time to second line therapy	Date of starting sunitinib treatment to the date further systemic therapy is started	2 years

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District
• Investigators: Principal Investigator: Howard Gurney, MBBS, FRACP, Crown Princess Mary Cancer Centre, Westmead

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (Estimate): October 22, 2012

Study Record Updates

• Last Update Posted (Estimate): May 15, 2014
• Last Update Submitted That Met QC Criteria: May 13, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Therapeutic Drug Monitoring; Pharmacokinetic; Renal Cell Carcinoma; Sunitinib; Treatment toxicity
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: HGWH008