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Malignant Solid TumourPhase 1NCT01286896

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

A Phase 1 study testing Sunitinib in people with Malignant Solid Tumour, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Solid Tumour
What is being tested?
Sunitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteNetherlands
Study dates
11 Apr 2011to 27 Dec 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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
  • 2.5 x ULN
  • Renal function as defined by serum creatinine => 1.5 x ULN or creatinine clearance => 50 mL/min (by Cockcroft-Gault formula);
  • No radio- or chemotherapy or other investigational drug treatment within the last 4 weeks prior to study entry, with the exception of palliative radiotherapy (8 Gy or on the extremities).

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

    Amsterdam, 1066CX

Other trials in Netherlands

About this study

Official title: Use of Individual PK-guided Sunitinib Dosing: A Feasibility Study in Patients With Advanced Solid Tumors

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.

Read the detailed description

Sunitinib is an orally available inhibitor of vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGF), cytokine receptor (c-KIT), and receptor tyrosine kinase (FLT-3) activity. Sunitinib is proven effective as single agent in several solid tumor types and is approved for use in advanced renal cell cancer (RCC) and imatinib-resistant or -intolerant gastrointestinal stromal tumors (GISTs). However, in a large percentage of patients (30 and 50%), dose reductions are required because of multiple grade 2 toxicities or due to grade 3 or 4 toxicities. Therefore, the currently used dosing schedule is not optimal.

Recently, a dose-efficacy relation was established for sunitinib treatment. This large meta-analysis of pharmacokinetic/pharmacodynamic data from studies performed in mRCC patients, GIST patients and patients with solid tumors, clearly showed a relationship between sunitinib exposure and efficacy and tolerability. Both time to progression (TTP) and overall survival (OS) were significantly better for mRCC patients with high area under the curve (AUC) compared to low AUC. This was not only observed for sunitinib exposure but also for its active metabolite SU12662. In addition, there was a significant relationship between exposure and probability of partial response (PR) or complete response (CR) in mRCC patients (p=0.00001), indicating that a dose intensity in patients should be as high as possible. Target plasma concentrations of sunitinib plus metabolite (N-desethyl sunitinib) are in the range of 50 to 100 ng/mL, as deduced from pharmacokinetic (PK) / pharmacodynamic (PD) preclinical data. Since the dose-efficacy relation for sunitinib treatment is solely established in a retrospective (meta-) analysis from patients treated in several studies, we propose to perform a prospective feasibility study in 30 patients with PK guided dosing of sunitinib. If PK guided once-daily continuous sunitinib dosing is feasible, a RCT in mRCC patients will be performed comparing PK guided dosing with a standard sunitinib dosing schedule.

Being tested
Sunitinib
Keywords
advanced solid tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SunitinibDrug

    Also called Sutent®, SU 11248

    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.

Study groups in NCT01286896
Study groupRoleWhat they receive
SunitinibExperimentalSunitinib is administered in oral capsules of 12.5 mg. Patients will start with a continuous once-daily dose of 37.5 mg.
Receives: Drug: Sunitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. objective response rate

    To determine the objective response rate, CT-scan and/or MRI-scans will be performed 8 weeks after initiation of therapy and thereafter every 12 weeks until documented disease progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

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

  2. time to tumor progression

    To determine the time from start of study treatment to first documentation of objective tumor progression defined by 1.1 RECIST criteria performing CT/MRI scans 8 weeks after initiation of therapy and thereafter every 12 weeks

    Measured: Until the disease progression, 1 year in average

  3. validating the associations between genetic markers

    To start with the validation of previously identified associations between genetic markers in the pharmacokinetic and pharmacodynamic pathways of sunitinib and the development of toxicities. At day 15 ± 1day, day 29 ± 1day and after 8 weeks ± 1day - PK: Fingerprick for dried blood spot analysis of total trough levels of sunitinib and SU12662.

    Once during cycle 1: EDTA blood samples for pharmacogenetic analyses

    Measured: C1 D15 and C1 D29 and after 8 weeks

  4. tumor biopsy and peripheral blood sample for DNA sequencing

    Seven days prior to study medication treatment the tumor boipsy and blood draw will be performed to support the validation of DNA sequencing of tissue derived from a tumor biopsy and to obtain the DNA profile of the patient's tumor in order to (i) identify correlations between the genetic profile of the tumor and toxicity and efficacy parameters of sunitinib , and (ii) identify patients who could have advantage of specific follow-up treatment strategies.

    Measured: Day -7

  5. Progression free survival

    Measuring the time between the study start and the RECIST defined disease progression on CT/MRI scans performed 8 weeks after initiation of therapy and thereafter every 12 weeks

    Measured: Untill disease progression, 1 year in average

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2011 (estimated)
  2. Study start11 Apr 2011
  3. Primary completion27 Dec 2011
  4. Study completion27 Dec 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01286896
Sponsor's protocol ID
M10PKS
Other IDs
2010-021454-20
Status last verified
Oct 2011
First submitted
14 Jan 2011
Last updated
10 Jul 2025
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sunitinib in people with Malignant Solid Tumour, run by The Netherlands Cancer Institute at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01286896.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.

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