Pazopanib Tolerability When Given With Food

NCT02138526 | Completed Phase 1

• 1 other identifier: UMCN-AKF-13.05
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cancer

Keywords

cancer; pazopanib; food; pharmacokinetics

Outcome Measures

Primary Outcomes (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)

  4 weeks

Secondary Outcomes (2)

• number of side effects

  2 months

• questionnaire

  2 months

Study Arms (2)

fasted

ACTIVE COMPARATOR

Intake of pazopanib in agreement with drug label - fasted state

Drug: pazopanib

Continental breakfast

EXPERIMENTAL

Intake of a reduced equivalent pazopanib dose with a continental breakfast

Drug: pazopanib; Other: continental breakfast

Interventions

pazopanib DRUG

pazopanib 800mg OD without food

Also known as: Votrient

Continental breakfast; fasted

continental breakfast OTHER

pazopanib 600mg OD with food

Continental breakfast

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

RadboudUMC

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 31125423 RESULT

• 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.

  PMID: 33428771 DERIVED

Related Links

• paper

MeSH Terms

Conditions

Neoplasms

Interventions

pazopanib

Study Officials

• Nielka P. van Erp, PharmD, PhD

  Department of Pharmacy, Radboudumc

  PRINCIPAL INVESTIGATOR

• Carla M.L. van Herpen, MD, PhD

  Department of Medical Oncology, Radboudumc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 14, 2014
• Study Start: June 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: October 19, 2020

Record last verified: 2019-01

Locations

NL (1)