Use of Individual Pharmacokinetically (PK)-Guided Sunitinib Dosing: A Feasibility Study in Patients With Advanced Solid Tumors

NCT01286896 | Completed Phase 1

• 2 other identifiers: M10PKS2010-021454-20
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this prospective study is to determine the safety and feasibility of pharmacokinetically (PK) guided dosing of sunitinib in 30 patients. At day 15 ± 1day, day 29 ± 1day and after 8 weeks ± 1day of sunitinib treatment sunitinib and SU12662 trough levels will be measured. Depending on the sunitinib and SU12662 trough levels (and toxicity) dose adjustments will be made.

Conditions

Malignant Solid Tumour

Keywords

advanced solid tumors

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  To determine the safety and feasibility of PK guided dosing of sunitinib, weekly physical examination, blood hematology and blood chemistry parameters in the first 2 cycles, and monthly thereafter, will guide the safety of the treatment.

  During treatment with sunitinib Adverse Events will be recorded up to 30 days after treatment. Patient will remain on treatment untill the disease progression, 1 year in average

Secondary Outcomes (5)

• objective response rate

  8 weeks after initiation and thereafter every 12 weeks until disease progression, 1 year in average

• time to tumor progression

  Until the disease progression, 1 year in average

• validating the associations between genetic markers

  C1 D15 and C1 D29 and after 8 weeks

• tumor biopsy and peripheral blood sample for DNA sequencing

  Day -7

• Progression free survival

  Untill disease progression, 1 year in average

Study Arms (1)

Sunitinib

EXPERIMENTAL

Sunitinib is administered in oral capsules of 12.5 mg. Patients will start with a continuous once-daily dose of 37.5 mg.

Drug: Sunitinib

Interventions

Sunitinib DRUG

Patients will start treatment with a continuous once-daily dose of 37.5 mg sunitinib. After 22 days the first dose modification will be performed based on the total trough levels (TTL) combined for sunitinib plus SU12662 as measured by dried blood spot (DBS) analyses taken at day 15 ± 1day. A second dose modification will be performed after 36 days (7 days after the first dose adjustment) based on the TTL taken at day 29 ± 1day. One treatment cycle is defined as 28 days. After 8 weeks a third analyses for TTL will be performed without further consequences for sunitinib dosing. Patients will be evaluated by CT- or MRI-scans for the response to therapy at week 8, and thereafter every 12 weeks. One blood sample will be harvested for pharmacogenetic analyses.

Also known as: Sutent®, SU 11248

Sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed advanced tumors for which sunitinib is considered standard or patients with advanced or metastatic tumors for whom no standard therapy is available;
• Age more then 18 years;
• Able and willing to give written informed consent;
• Able and willing to undergo blood sampling for pharmacogenetic and pharmacokinetic analysis;
• Able and willing to undergo a tumor biopsy for DNA sequencing;
• Able to swallow oral medications
• Life expectancy more then 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity;
• WHO performance status of 0 or 1;
• Evaluable disease according to RECIST 1.1 criteria;
• Minimal acceptable safety laboratory values
• ANC of =\> 1.5 x 109 /L
• Platelet count of =\> 100 x 109 /L
• Hepatic function as defined by serum bilirubin =\> 1.5 x ULN, ASAT and ALAT
• x ULN
• Renal function as defined by serum creatinine =\> 1.5 x ULN or creatinine clearance =\> 50 mL/min (by Cockcroft-Gault formula);

You may not qualify if:

• Current treatment in another therapeutic clinical trial
• Congestive heart failure, myocardial infarction or coronary artery bypass graft in the previous six months, ongoing severe or unstable angina or any unstable arrhythmia requiring medication
• Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up
• Women who are pregnant or breast feeding.
• Both men and women enrolled in this trial must agree to use a reliable contraceptive method throughout the study (definition of adequate contraceptive methods will be based on the judgment of the principal investigator or a designated associate).
• Legal incapacity
• Known allergy/intolerance to sunitinib or any of the excipients

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Pfizer: collaborator

Study Sites (1)

The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, 1066CX, Netherlands

Location

MeSH Terms

Interventions

Sunitinib

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Neeltje Steeghs, Md, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2011
• First Posted: January 31, 2011
• Study Start: April 11, 2011
• Primary Completion: December 27, 2011
• Study Completion: December 27, 2011
• Last Updated: July 10, 2025

Record last verified: 2011-10

Locations

NL (1)