Clinical Trials Register

Summary
EudraCT Number:	2011-001211-31
Sponsor's Protocol Code Number:	RG_10-177
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:	2012-01-24
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

2011-001211-31

A.3

Full title of the trial

A study of pazopanib efficacy and safety in patients with advanced clear-cell renal cell carcinoma and ECOG Performance Status 2 (PaZ02)

A.3.1

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

A study of the effectiveness and safety of the drug Pazopanib for use in patients with advanced kidney cancer who are suffering symptoms from their illness.

A.3.2

Name or abbreviated title of the trial where available

Pazopanib in patients with renal cancer (PaZ02)

A.4.1

Sponsor's protocol code number

RG_10-177

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	University of Birmingham
B.1.3.4	Country	United Kingdom
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	GlaxoSmithKline
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Birmingham
B.5.2	Functional name of contact point	Brendan Laverty
B.5.3	Address:
B.5.3.1	Street Address	(as previous)

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 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.3.1	Product name	pazopanib
D.3.2	Product code	not applicable
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 hydrochloride
D.3.9.1	CAS number	635702-64-6
D.3.9.3	Other descriptive name	Votrient
D.3.9.4	EV Substance Code	AS1
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Clear cell renal cell carcinoma

E.1.1.1

Medical condition in easily understood language

Cancer of the kidneys

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10038416
E.1.2	Term	Renal clear 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

The main objective of our clinical trial is to find out whether treatment with a drug called pazopanib is beneficial and safe for patients with advanced renal cancer and poor clinical condition (‘poor performance status’). These patients are often deemed not fit for treatment because of their poor prognosis and because of their perceived inability to withstand the side effects of the therapy. The treatments currently available cause severe side effects in two thirds of the patients and may require frequent hospital visits. By contrast pazopanib has demonstrated a significant efficacy and is well tolerated therefore it may represent a valuable treatment option for renal cancer patients with poor performance status. To assess treatment efficacy we will study in what percentage of patients pazopanib is able to prevent further tumour growth for at least 6 months; to assess safety we will study the ratio of patients who develop severe, drug induced, toxicity.

E.2.2

Secondary objectives of the trial

The secondary research objectives of our clinical trial are: i) To study the duration of survival from the start of the treatment with pazopanib until death of renal cancer patients with poor performance status (technically called ‘Overall Survival’). ii) To study the length of time over which pazopanib is able to block the growth of the renal cancer (technically called ‘Progression Free Survival’). iii) To study the ability of pazopanib to induce a shrinkage of the tumour mass (technically called ‘Response Rate’). iv) To study the entire profile of the side effects induced by pazopanib in the same group of patients. v) To study the differences between the drug dose actually administered compared with the planned dose.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Written informed consent 2) Histologically confirmed diagnosis of renal cell carcinoma with clear cell component 3) Locally advanced (defined as not amenable of curative surgery) or metastatic disease 4) Measurable disease as per RECIST Criteria 1.1 5) Performance Status 2 assessed using the ECOG scale. 6) No prior systemic therapy 7) Female patients of childbearing potential will be eligible if they agree to adequate contraception. Pregnancy test must be negative 1 week before first drug dose 8) Adequate organ function as defined by the following criteria: o Total serum bilirubin ≤1.5 x ULN. Patients with Gilbert’s disease are eligible if the total; bilirubin is <3.0 x ULN and direct bilirubin is ≤35%. o Serum transaminases (AST and ALT) <2.5 x ULN, unless liver metastases are documented in which case AST and ALT must be ≤ 5 x ULN oCalculated creatinine clearance ≥30mL/min (Cockroft Gault method) oUrine Protein to Creatinine Ratio (UPC) < 1. If UPC ≥ 1 then a 24 hour urine protein must be assessed. Only patients with 24 hour urine protein < 1g will be eligible oTotal serum calcium concentration < 2.9 mmol/l oAbsolute neutrophil count (ANC) ≥1500/mm3 oHaemoglobin ≥ 9g/dl oPlatelets ≥ 100,000/mm3 oINR (International Normalised ratio) ≤ 1.2 x ULN. Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range. 9) Age ≥18 10)Life expectancy ≥ 12 weeks 11)Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

E.4

Principal exclusion criteria

1) Pregnant or lactating female patients. Patients who agree to discontinue nursing 14 days prior to commencing treatment and do not nurse throughout all the treatment period are eligible 2) Previous systemic treatment for RCC (licensed or investigational) including adjuvant or neo-adjuvant therapy 3) Major surgery or trauma < 4 weeks or radiotherapy and/or presence of any non-healing wound, fracture, or ulcer. Radiotherapy < 2 weeks prior to starting treatment 4) History or clinical evidence of brain metastases or active seizure disorders 5) Previous malignancies within the last 5 years, with the exception of successfully treated superficial or in situ carcinomas and of invasive tumours treated with curative intent and in remission for at least 5 years 6) Current use of drugs which are known strong CYP4A inhibitors (7.10) 7) Use of any prohibited medications within 14 days of the first dose of study medication (7.11) 8) Uncontrolled hypertension defined as systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 95 mm Hg. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry 9) Presence of uncontrolled infection 10)Prolongation of the QT interval (QTc) > 480 msecs 11)History of malabsorption, major gastrointestinal tract resection or other pathology likely to affect study drug absorption 12)History of any one or more of the following cardiovascular conditions within the past 6 months: o Cardiac angioplasty or stenting o Myocardial infarction o Unstable angina o Coronary artery by-pass graft surgery o Symptomatic peripheral vascular disease o Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) Functional Classification 13)History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) within the past 12 months 14)History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Patients with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible 15)Evidence of active bleeding or bleeding diathesis 16)Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels 17)Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study 18)Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drug chemically related to pazopanib

E.5 End points

E.5.1

Primary end point(s)

1) Tolerability - will be assessed as the proportion of patients who have not developed grade 3 or 4 clinically relevant and drug related adverse events within 6-months from the date of entry into the trial. Any adverse event to be classified ‘Clinically Relevant’ and to be included in the analysis of the primary tolerability endpoint will need to satisfy all the following definitions: • Adverse events which are Grade 3 or Grade 4 in severity according to the CTCAE version 4. • Adverse events which in the opinion of the Investigator are definitely related, probably related and possibly related to the drug treatment. Adverse events which are unrelated or unlikely to be related will not be included in the analysis. • Adverse events which are symptomatic and in the opinion of the Investigator affect the patient’s wellbeing including but not limited to: o Adverse events which result in Serious Adverse Events o Adverse events which lead to a permanent drug discontinuation o Adverse events which result in a decrease of the patient’s performance status 2) Efficacy - will be assessed as the proportion of all patients who entered the trial and who are progression free at 6 months. Disease Progression will be assessed as defined by RECIST Criteria 1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

The end of trial will be at the point when all patients have a minimum of 12 months follow-up from registration. This will allow sufficient time for the completion of protocol procedures, data collection and data input. The Trials Office will notify the MHRA and main REC that the trial has ended and will provide them with a summary of the clinical trial report within 12 months of the end of trial.

E.5.2

Secondary end point(s)

Progression free survival (PFS) will be measured at 12 months post registration as the number of whole days from the date of entry into trial until evidence of radiological disease progression or death by any cause, or censor date. Overall survival (OS) will be measured at 12 months post registration as the number of whole days from date of entry into the trial until death by any cause or censor. Response Rate will be defined as the proportion of patients who achieve either a complete or partial Radiological Response and Clinical benefit rate will be defined as the proportion of patients who achieve either a complete, partial or stable radiological response as defined by the RECIST 1.1 Criteria. Duration of response will be measured as the number of whole days between date of first evidence of response (CR or PR) until date of Progression of the Disease (PD) or death as defined by the RECIST 1.1 Criteria. Treatment safety is defined as the proportion of patients developing Adverse Events (AEs). Adverse Events will be collected from the date of entry in the trial until 28 days after drug discontinuation and graded according the NCI-CTC version 4. Adverse Events will be classified by causality, grade, type, duration and system involved. Drug dose administered will be defined by dose intensity, incidences of dose reductions, interruptions, escalations and discontinuations.

E.5.2.1

Timepoint(s) of evaluation of this end point

As above

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

E.6.7

Pharmacodynamic

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)

E.8.2.2

Placebo

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

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

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

The end of trial will be 12 months after the last patient registered.

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