Clinical Trials Register

Summary
EudraCT Number:	2013-004108-20
Sponsor's Protocol Code Number:	UMCN-AKF13.05
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2013-004108-20

A.3

Full title of the trial

Improving the tolerability of the oral targeted anti-cancer drug pazopanib by food intake (DIET)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

To study the effect of food on the absorption of pazopanib and on the occurence of side effects when pazopanib is ingested with food.

A.3.2

Name or abbreviated title of the trial where available

DIET

A.4.1

Sponsor's protocol code number

UMCN-AKF13.05

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Radboud University Nijmegen Medical Centre
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Radboud University Nijmegen Medical Centre
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Radboud University Nijmegen Medical Centre
B.5.2	Functional name of contact point	Angela Colbers
B.5.3	Address:
B.5.3.1	Street Address	Geert Grooteplein 100
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6525 GA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31243616405
B.5.5	Fax number	+31243668755
B.5.6	E-mail	a.colbers@akf.umcn.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Votrient
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Group Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients who are treated or will be treated with pazopanib.

E.1.1.1

Medical condition in easily understood language

Patients who are treated or will be treated with pazopanib.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10067946
E.1.2	Term	Renal cell carcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10073145
E.1.2	Term	Soft tissue cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A: To determine the equivalent dose of pazopanib when taken with a continental breakfast compared to 800 mg in fasted state.
Part B:To evaluate whether food can reduce the side effects diarrhea and nausea.

E.2.2

Secondary objectives of the trial

Part A: To monitor the occurrence of adverse events of pazopanib with and without food according to the CTC-AE criteria v 4.03.
Part B: To evaluate the preference of the patients: intake of pazopanib with or without food.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) 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.
1) ≥ 18 year old men and women who use pazopanib for soft tissue sarcoma or metastatic renal cell carcinoma
2) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
3) BMI between 18-30 kg/m2
4) Adequate organ system function
bsolute neutrophil count (ANC) >1.5 X 109/L
Hemoglobina >9 g/dL (5.6 mmol/L)
Platelets >100 X 109/L
Total bilirubin <2 X ULN
Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)c <3 X ULN
Serum creatinine <1.5 mg/dL (133 µmol/L)
Or, if >1.5 mg/dL: Calculated creatinine clearance (ClCR) >30 mL/min

E.4

Principal exclusion criteria

1) Poorly controlled hypertension; systolic blood pressure ≥ 40 mm Hg or diastolic blood pressure ≥ 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.
2) Corrected QT interval (QTc) > 480msecs.
3) 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)
4) 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.
5) 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.
6) 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.
7) 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).
8) Evidence of active bleeding or bleeding diathesis.
9) 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 vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
10) Recent hemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug).
11) 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.
12) Unable or unwilling to discontinue use of prohibited medications listed in protocol APPENDIX 5 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.
13) 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 (
14) Women of childbearing potential without adequate contraception, pregnant or breastfeeding women.

E.5 End points

E.5.1

Primary end point(s)

Part A: The aim of this study to show that a dose reduction of pazopanib is possible when ingested with a regular continental breakfast to maintain equivalent AUC compared to 800 mg pazopanib ingested in a fasted state.
Part B: The aim of this study is to show a difference is the occurrence of side effects (e.g. diarrhea and nausea) when a reduced dose of pazopanib is ingested with food.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A: after trial day 29
Part B: after trial day 61

E.5.2

Secondary end point(s)

Part A: To explore, quantify and describe the correlation in the occurrence of side effects when pazopanib is ingested with food.
Part B: To explore, quantify and describe the correlation in patients own preference between ingesting pazopanib with and without food.

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A: after trial day 29
Part B: after trial day 61

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

Yes

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

open, cross-over (patient is his/her own control)

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

patients are their own control

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Part A: last patient trial day 29
Part B: last patient trial day 61

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1