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CancerPhase 1DIETNCT02138526

Pazopanib Tolerability When Given With Food

A Phase 1 study testing pazopanib and continental breakfast in people with Cancer, run by Radboud University Medical Center 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

Pazopanib (Votrient) is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg once daily (OD) regardless of size, age and clinical condition. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
pazopanib and continental breakfast
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
1 siteNetherlands
Study dates
Jun 2014to Nov 2018
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

  • Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
  • Note: informed consent may be obtained prior to start of the specified screening window.
  • Note: procedures conducted as part of the subject's routine clinical management (e.g. blood count) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
  • ≥ 18 year old men and women who use pazopanib
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Adequate organ system function

Who cannot join

  • Poorly controlled hypertension; systolic blood pressure (SBP) ≥ 40 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg.
  • Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study.
  • Corrected QT interval (QTc) > 480msecs.
  • History of any one or more of the following cardiovascular conditions within the past 6 months:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
Show all 30Show fewer
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesion/s with risk of bleeding
  • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation.
  • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
  • Malabsorption syndrome.
  • Major resection of the stomach or small bowel.
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
  • Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
  • Evidence of active bleeding or bleeding diathesis.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
  • Note: Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessel is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
  • Recent hemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug).
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of day 1 and for the duration of the study.
  • Concurrent use of other substances known or likely to interfere with the pharmacokinetics of pazopanib.
  • Patients, who are adjusted to proton pump inhibitors and had no dose modifications for over two weeks, are allowed to participate
  • Women of childbearing potential without adequate contraception, pregnant or breastfeeding women.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • RadboudUMC

    Nijmegen, Gelderland, 6500 HB

Other trials in Netherlands

About this study

Official title: Improving the Tolerability of the Oral Targeted Anticancer Drug Pazopanib by Food Intake (DIET)

Pazopanib (Votrient) is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg once daily (OD) regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of ~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A reduced dose taken with food could be a possible approach to reduce these side effects. Therefore the investigators initially want to determine the equivalent reduced dose of pazopanib when taken with a continental breakfast. Thereafter the investigators want to investigate whether the intake with food reduces the frequently reported side effects nausea and diarrhea.

Read the detailed description

Pazopanib (Votrient) is a multi targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor, (VEGFR-1, -2 en -3), platelet-derived growth factor receptor (PDGFR-α and -β), and stem cell factor receptor (c-KIT). Pazopanib is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg OD regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of ~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A dose reduction when ingested with food could be a logical approach to reduce these side effects; however this is not tested in patients yet. Therefore we want to perform a bioequivalent study to investigate what dose with a continental breakfast equals the dose of 800 mg in fasted conditions (study part A). In part B of the study we want to investigate whether the intake with food reduces the frequently reported side effects.

Conditions
Cancer
Being tested
pazopanib, continental breakfast
Keywords
cancer, pazopanib, food, pharmacokinetics
Medical subject headings
Neoplasms

What participants receive

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

  • pazopanibDrug

    Also called Votrient

    pazopanib 800mg OD without food

  • continental breakfastOther

    pazopanib 600mg OD with food

Study groups in NCT02138526
Study groupRoleWhat they receive
fastedActive comparatorIntake of pazopanib in agreement with drug label - fasted state
Receives: Drug: pazopanib
Continental breakfastExperimentalIntake of a reduced equivalent pazopanib dose with a continental breakfast
Receives: Drug: pazopanib; Other: continental breakfast

What is being measured

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

  1. Area under the plasma concentration versus time curve (AUC) of pazopanib

    Determination of AUC of pazopanib when taken with a continental breakfast compared to 800 mg in fasted state (geometric mean ratio will be determined)

    Measured: 4 weeks

Secondary outcomes (2)

  1. number of side effects

    Number of side effects will be compared for the two treatments (with and food.

    Measured: 2 months

  2. questionnaire

    Preference of patients (by questionnaire): intake of pazopanib with or without

    Measured: 2 months

Timeline

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

  1. First posted14 May 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionNov 2018
  4. Study completionNov 2018

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
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02138526
Sponsor's protocol ID
UMCN-AKF-13.05
Acronym
DIET
Status last verified
Jan 2019
First submitted
29 Apr 2014
Last updated
19 Oct 2020
Results posted
No
Data monitoring committee
No

Publications

  • Lubberman FJE, Gelderblom H, Hamberg P, Vervenne WL, Mulder SF, Jansman FGA, Colbers A, van der Graaf WTA, Burger DM, Luelmo S, Moes DJAR, van Herpen CML, van Erp NP. The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (DIET Study). Clin Pharmacol Ther. 2019 Nov;106(5):1076-1082. doi: 10.1002/cpt.1515. Epub 2019 Jul 9.

    PubMed 31125423

  • Krens SD, Lubberman FJE, van Egmond M, Jansman FGA, Burger DM, Hamberg P, Vervenne WL, Gelderblom H, van der Graaf WTA, Desar IME, van Herpen CML, van Erp NP. The impact of a 1-hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure. Int J Cancer. 2021 Jun 1;148(11):2799-2806. doi: 10.1002/ijc.33469. Epub 2021 Jan 19.

    PubMed 33428771

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing pazopanib and continental breakfast in people with Cancer, run by Radboud University Medical Center 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 6 inclusion and 30 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 19 Oct 2020. 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?

Area under the plasma concentration versus time curve (AUC) of pazopanib (time frame: 4 weeks). 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 NCT02138526, which also lists 2 linked publications.

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 19 Oct 2020.

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Pazopanib Tolerability When Given With Food | AzTrials