Clinical Trials Register

Summary
EudraCT Number:	2010-020965-26
Sponsor's Protocol Code Number:	VEG113387
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-09-16
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

Czechia - SUKL

A.2

EudraCT number

2010-020965-26

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled phase III study to evaluate the efficacy and safety of pazopanib as adjuvant therapy for subjects with localized or locally advanced RCC following nephrectomy

Randomizované, dvojitě zaslepené, placebem kontrolované klinické hodnocení hodnotící účinnost a bezpečnost pazopanibu v adjuvatní léčbě u pacientů s lokalizovaným nebo lokálně pokoročilým karcinomem z renálních buněk, kteří jsou po nefrektomii

A.3.1

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

A study to test whether pazopanib can prevent or delay kidney tumor coming back after the tumor has been removed

A.3.2

Name or abbreviated title of the trial where available

VEG113387

A.4.1

Sponsor's protocol code number

VEG113387

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	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma Services AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1 Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+4161324 1111
B.5.5	Fax number	+4161324 8001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

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.3.1	Product name	Votrient (GW786034)
D.3.2	Product code	Votrient (GW786034)
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
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	444731-52-6
D.3.9.2	Current sponsor code	GW786034
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)	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Renal Cell carcinoma

E.1.1.1

Medical condition in easily understood language

Renal Cancer

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10038415
E.1.2	Term	Renal cell carcinoma stage unspecified
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	20.0
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate disease-free survival (DFS) with pazopanib 600 mg daily initial dose as compared to placebo as adjuvant therapy for subjects with localized/locally advanced RCC following nephrectomy.

E.2.2

Secondary objectives of the trial

Efficacy objectives:•To evaluate OS and DFS rates at yearly time points (e.g.1 year, 2 years,etc)with pazopanib 600 mg daily initial dose compared to placebo.
•To evaluate efficacy endpoints: DFS,OS and DFS rates at yearly time points,with pazopanib compared to placebo as adjuvant RCC treatment in all subjects(regardless of whether 600 mg or 800 mg daily initial dose is used).
•To evaluate efficacy endpoints DFS and OS with pazopanib 800 mg daily initial dose compared to placebo.
Safety objective:
•To evaluate safety and tolerability in subjects treated with pazopanib 600 mg daily initial dose compare to those treated with placebo.
•To evaluate safety and tolerability in subjects treated with pazopanib compared to those treated with placebo in all subjects (regardless of whether 600mg or 800 mg daily initial dose is used).
•To summarize selected safety and tolerability parameters in subjects treated with pazopanib 800mg daily initial dose compared to those treated with placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed written informed consent
2. Diagnosis of RCC with clear-cell or predominant clear-cell histology.
3. Subjects with non-metastatic disease (M0) fulfilling any of the
following combinations of pathologic staging based on AJCC TNM staging
version 2010 and Fuhrman nuclear grading [see Section 12.2 Appendix 2
and Section 12.3 Appendix 3 for details].
• pT2, G3 or G4, N0; or,
• pT3, Gany, N0; or,
• pT4, Gany, N0; or,
• pTany, Gany, N1
Note 1: Excisional biopsy is required of all regional lymph node(s) which
appear abnormal on pre-operative scans or at surgery.
In order to properly stratify subjects (see Section 5.5), it is required that
the investigator designate the nodal status as either N0 or N1 according
to the following criteria which will be captured in the eCRF:
N0 requires that a subject have no abnormal regional lymph nodes on
preoperative scans or visualized at surgery, OR have regional lymph
nodes biopsied with negative (no tumor present) result.
N1 requires that a subject have regional lymph nodes biopsied with
positive (tumor present) result.
Note 2: Subjects with ipsilateral multicentric RCC are eligible if the most
advanced lesion per pT stage fulfils any of the aforementioned
combinations of pathologic staging and Fuhrman nuclear grading.
4. Fulfill all of the following criteria of disease-free status at baseline:
• Had complete gross surgical resection of all RCC via nephrectomy.
• Baseline imaging of chest, abdomen and pelvis shows no metastasis or
residual tumor lesions as confirmed centrally by an independent
radiologist.
Note: As noted above, excisional biopsy is required of all regional lymph
node(s) which appear abnormal on pre-operative scans or at surgery. In
event lymphadenectomy was not performed during surgery, subjects
with one or more regional lymph nodes identified with short axis of ≥
15mm by Independent Central Imaging Review of the baseline scans are
considered to have gross residual disease
and therefore ineligible. See Section 7.5.3 for Guideline of Imaging
Diagnosis for Baseline Disease-free Status.
5. Received no prior adjuvant or neo-adjuvant treatment for RCC.
6. Recovered from nephrectomy: any surgery related toxicities should be
reduced to ≤ grade 1 per NCI CTCAE (Version 4)
7. Karnofsky performance scale (KPS) of ≥ 80.
8. Adequate organ system function as defined in Table 3, page 26 of
Protocol 02
9. Male or female, age ≥ 18 years
Note 1: Female subjects of childbearing potential must have a negative
serum or unrine pregnancy test within 7 days of the first dose of study
treatment and agree to
use an effective contraception method, as described in Section 7.6.7.1,
during Study Treatment Period until 14 days following the last dose of
study treatment.
Refer to Section 7.6.7.1 for the definitions of female of childbearing
potential and female of non-childbearing potential.
Note 2: Female subjects who are lactating must discontinue nursing
prior to the first dose of study treatment and refrain from nursing
throughout the study treatment
period until 14 days following the last dose of study treatment.

E.4

Principal exclusion criteria

Subjects meeting any of the following criteria must not be enrolled in the
study:
1. Locally recurrent RCC, bilateral RCC, or history of another malignancy
Exception: Subjects who have had another malignancy and have been
disease-free for 5 years, or subjects with a history of completely
resected non-melanomatous skin carcinoma or successfully treated in
situ carcinoma are eligible.
2. Clinically significant gastrointestinal abnormalities that may increase
the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• 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 intraabdominal
abscess within 28 days prior to beginning study treatment
3. Active diarrhea of any grade
4. 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 resulting in dumping
syndrome or clinical signs of malabsorption
5. History of human immunodeficiency virus (HIV) infection.
6. History of chronic active hepatitis including subjects who are carriers
of hepatitis B virus (HBV) or hepatitis C virus (HCV)
7. Presence of uncontrolled infection.
8. 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 arterial vascular disease
9. History of Class III or IV congestive heart failure, as defined by the
New York Heart Association Classification of Congestive Heart Failure
[See Section 12.7 Appendix 7 for description]
10. 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
anticoagulating agents for at least 6 weeks are eligible
11. Corrected QT interval (QTc) > 480 milliseconds (msec)
12. Poorly controlled hypertension, defined as systolic blood pressure
(SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg.
Note: Screening/Baseline blood pressure (BP) must be assessed with
three measurements at approximately 2-minute intervals. The mean SBP
/ DBP values from the three readings must be <140/90 mmHg in order
for a subject to be eligible for the study (see Section 7.6.2 for instruction
on blood pressure measurement and obtaining mean blood pressure
values).
If the subject's initial screening SBP/DBP is ≥ 140/90mmHg, initiation
or adjustment of antihypertensive medication(s) is permitted in an
attempt to control the subject's BP level to below 140/90mmHg. Once
the subject's BP level is wellcontrolled, BP must be re-assessed with
three measurements at approximately 2- minute intervals and the mean
SBP/DBP from this reassessment must be <140/90mmHg in order for
subject to be eligible. At least 24 hours must have elapsed between antihypertensive
medication initiation or adjustment and BP reassessment.
The final reassessed BP values should be entered into eCRF as baseline.
13. Evidence of active bleeding or bleeding diathesis
14. 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.
15. Unable or unwilling to discontinue use of prohibited medications list
in Section 6.3
for at least 14 days or five half-lives of a drug (whichever is longer) prior
to the first dose of study treatment and for the duration of the study.
16. Concurrent therapy given to treat cancer including treatment with an
investigational agent or concurrent participation in another clinical trial
involving anti-cancer
investigational drug.
17. Administration of any investigational drug within 30 days or 5 halflives,
whichever
is longer, preceding the first dose of study treatment.
18. Have a known immediate or delayed hypersensitivity reaction or
idiosyncrasy to drugs chemically related to pazopanib or excipients that
in the opinion of the investigator contraindicates their participation.
19. Prior or current use of systemic anti-VEGF inhibitors, cytokines (e.g.
interferon, interleukin 2).

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint of this study is DFS, which is defined as time from randomization to developing local disease recurrence and/or metastasis, or death due to any cause whichever comes first

E.5.1.1

Timepoint(s) of evaluation of this end point

Imaging assessments are the major evaluations for DFS, which will be done at baseline, week 20, 36, 52, every 6 months between year 2-5, then yearly thereafter until study reached the clinical cutoff for DFS.

E.5.2

Secondary end point(s)

The secondary endpoints include:
- OS, defined as time from randomization to death due to any cause.
- DFS rates at yearly time points (e.g. 1 year, 2 years, etc.). Actual time points will depend on data maturity at the time of the DFS analysis
- The safety endpoints include the incidence, severity and causality of all AE, SAE and other safety parameters during treatment period. Long term safety will also be analyzed.
- Change from baseline in subject self-reports on health outcome and quality of life as measured by Cancer Therapy-Kidney Symptom Index -19 (FKSI-19) and EuroQOL (EQ-5D), respectively.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Overall survival, defined as the interval from randomization to death due to any cause

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

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.5

Parallel group

Yes

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

167

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Yes

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

15-April-2019

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.1.2.1

Number of subjects for this age range:

1200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

300

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

690

F.4.2.2

In the whole clinical trial

1500

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)

Subsequent adjuvant treatments for RCC are not allowed. Once a subject has objective evidence of disease recurrence, he/she should receive the first-line treatment for metastatic RCC per local standard.
After discontinuation from or completion of the study, subjects can receive further treatment at the discretion of the subjects and their treating physicians.

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

2010-10-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-11-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-15

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