Clinical Trials Register

Summary
EudraCT Number:	2008-005053-38
Sponsor's Protocol Code Number:	VDF111687
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-04-16
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

UK - MHRA

A.2

EudraCT number

2008-005053-38

A.3

Full title of the trial

An open-label study to investigate the pharmacodynamics of a repeat dose regimen of bevacizumab (10mg/kg q2w) and escalating repeat doses of pazopanib in renal cell carcinoma

A.4.1

Sponsor's protocol code number

VDF111687

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research & Development Ltd.
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/06/382
D.3 Description of the IMP
D.3.1	Product name	pazopanib
D.3.2	Product code	GW786034
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	pazopanib
D.3.9.1	CAS number	635702-64-6
D.3.9.2	Current sponsor code	GW786034
D.3.9.3	Other descriptive name	pazopanib hydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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.IMP: 2
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/06/382
D.3 Description of the IMP
D.3.1	Product name	pazopanib
D.3.2	Product code	GW786034
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	pazopanib
D.3.9.1	CAS number	635702-64-6
D.3.9.2	Current sponsor code	GW786034
D.3.9.3	Other descriptive name	pazopanib hydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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.IMP: 3
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	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bevacizumab
D.3.9.1	CAS number	216974-75-3
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Metastatic Renal Cell Carcinoma

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10050513
E.1.2	Term	Metastatic renal cell carcinoma

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To estimate the pharmacodynamic effect of bevacizumab (10mg/kg q2w) on various tumour characteristics in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy.

E.2.2

Secondary objectives of the trial

To compare the pharmacodynamic effects of repeat-dose bevacizumab (10mg/kg q2w) versus repeat-dose pazopanib (800 mg qd) in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy.
To evaluate the safety and tolerability of repeat-dose bevacizumab (10mg/kg q2w) in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy.
To evaluate the safety and tolerability of repeat-dose pazopanib (200mg twice weekly to 1200 mg qd) in subjects with renal cell carcinoma who experience tumour progression on previous first-line (or greater) therapy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part I
1. Histologically or cytologically confirmed unresectable RCC with a clear cell component.
2. Experienced documented evidence of radiological progression based on [RECIST] while on first line (or greater) RCC therapy and within 6 months prior to the first dose of study medication (bevacizumab).
3. Evidence of unidimensionally measurable disease.
4. Free of any malignant disease other than RCC for at least 5 years prior to the first dose of (bevacizumab) in this study, with the exception of the following: Cervical carcinoma in situ, Melanoma in situ,Basal or squamous cell carcinoma of the skin
5. ECOG Performance Status of 0 to 1.
6. Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedures to NCI CTCAE Grade 1 or less.
7. Adequate organ function, as defined by the protocol.
8. Males and females ≥ 18 years of age at screening.

Part II
1. The subject met all eligibility criteria in Part I of the study.
2. The subject would derive continued therapeutic benefit from anti-angiogenic therapy.
3. There are no safety concerns that would present an unacceptable benefit-risk profile for treatment with pazopanib.

E.4

Principal exclusion criteria

1. Cancer metastatic to the central nervous system or leptomeningeal carcinomatosis.
2. Previous treatment with bevacizumab or pazopanib.
3. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bevacizumab or pazopanib or components of bevacizumab or pazopanib (other than active drugs).
4. Anticancer therapy (radiotherapy, chemotherapy, or immunotherapy) within 28 days prior to the first dose of study medication and through completion of all study procedures.
5. Use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study medication.
6. Assessable disease is unsuitable for biopsy or the patient is unwilling or not sufficiently fit to undergo serial biopsies.
7. Major surgical procedure or traumatic injury within 28 days prior to the first dose of study medication (bevacizumab).
8. Evidence of active bleeding or bleeding diathesis, or any serious, non-healing wound, ulcer, or bone fracture.
9. Hemoptysis within 6 weeks of the first dose of study medication.
10. Use of therapeutic doses of warfarin within 5 half-lives of the first dose of study medication and during treatment in the study
11. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days of the first dose of study medication.
12. Clinically significant gastrointestinal abnormalities.
13. Known endobronchial lesions or involvement of large pulmonary vessels by tumor.
14. Active or uncontrolled infection at the time of first dose of study medication.
15. Prolongation of corrected QT interval (QTc) >480 milliseconds (msec).
16. Positive test result for (HIV) antibody.
17. Any of the following within 6 months prior to the first dose of study medication (bevacizumab): Cardiac angioplasty or stenting, Severe and/or unstable angina, Myocardial infarction, Coronary artery bypass graft (CABG), Class III or IV congestive heart failure, Symptomatic peripheral vascular disease, Cardiac dysrhythmias of NCI CTCAE Grade 2 or greater and atrial fibrillation of any grade.
18. History of cerebrovascular accident or transient ischemic attack
19. Poorly controlled hypertension.
20. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
21. Internal metal medical devices or other metal items that may place the subject's health at risk and/or interfere with MRI scans.
22. History of hypersensitivity to gadolinium or other intravenous dye contrast agents.
23. History of hypersensitivity to iodine-based contrast agents or history of severe asthma.
24. Pregnant or lactating females.
25. Any serious and/or unstable pre-existing medical, psychiatric, or other condition.

E.5 End points

E.5.1

Primary end point(s)

Primary pharmacodynamic endpoints for bevacizumab in Part I will include the following, as data permit:
1. Tumour size, as measured by the sum of the longest diameters of all target lesions on CT and expressed as a percent reduction from baseline.
2. Tumour perfusion, as assessed by the estimation of Ktrans by DCE-MRI.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

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)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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.8.4.1

Number of sites anticipated in 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

Information not present in EudraCT

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

Last subject last visit, as defined in the protocol

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Once particpation in the trial has ended, treatment of the patient will be determined by the attending physician.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-04-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-06-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-11-01

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