Clinical Trials Register

Summary
EudraCT Number:	2011-004562-16
Sponsor's Protocol Code Number:	ICR-CTSU/2011/10033
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-05-09
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

2011-004562-16

A.3

Full title of the trial

A Phase II Study of Axitinib in Patients with Metastatic Renal Cell Cancer Unsuitable for Nephrectomy

A.3.1

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

Axitinib Treatment for Widespread Kidney Cancer Unsuitable for Surgery

A.3.2

Name or abbreviated title of the trial where available

A-PREDICT

A.4.1

Sponsor's protocol code number

ICR-CTSU/2011/10033

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN72679844

A.5.4

Other Identifiers

Name:	Sponsor Identification Number	Number:	CCR3587
Name:	ICR-CTSU Protocol Number	Number:	ICR-CTSU/2011/10033

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	Institute of Cancer Research
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	Pfizer Ltd
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Cancer Research UK
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	The Institute of Cancer Research
B.5.2	Functional name of contact point	Rachel Todd
B.5.3	Address:
B.5.3.1	Street Address	ICR Clinical Trials & Statistics Unit (ICR-CTSU)
B.5.3.2	Town/ city	The Institute of Cancer Research
B.5.3.3	Post code	SM2 5NG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02087224315
B.5.5	Fax number	0208 770 7876
B.5.6	E-mail	apredict-icrctsu@icr.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	The Royal Marsden Hospital NHS Foundation Trust
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	See above
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	The Institute of Cancer Research
B.5.2	Functional name of contact point	Rachel Todd
B.5.3	Address:
B.5.3.1	Street Address	ICR-CTSU, 15 Cotswold Road
B.5.3.2	Town/ city	Sutton, Surrey
B.5.3.3	Post code	SM2 5NG
B.5.4	Telephone number	02087224315
B.5.5	Fax number	0208 770 7876
B.5.6	E-mail	apredict-icrctsu@icr.ac.uk

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Axitinib
D.3.2	Product code	AG-013736
D.3.4	Pharmaceutical form	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	Axitinib
D.3.9.1	CAS number	319460-85-0
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	1 to 5
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

Metastatic renal cell carcinoma

E.1.1.1

Medical condition in easily understood language

Widespread kidney 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	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10050076
E.1.2	Term	Metastatic renal carcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Does treatment with axitinib stop previously untreated widespread kidney cancer that can't be surgically removed from getting worse for at least 6 months?

E.2.2

Secondary objectives of the trial

SECONDARY RESEARCH QUESTIONS:
What is the largest reduction in a participant's cancer seen during treatment with axitinib?

How long does treatment with axitinib stop participants' cancer from getting worse?

How long does treatment with axitinib keep people alive?

What are the side effects of treatment with axitinib in this group of patients?

How many participants' will be able to have surgery to remove their kidney due to treatment with axitinib?

EXPLORATORY QUESTION:
Are there biological or genetic markers that could be used to indicate who will respond best to axitinib treatment in future?

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A-PREDICT Translational Study
A key aim of this study is to evaluate changes in circulating and tumour biomarkers in relation to tumour response.

E.3

Principal inclusion criteria

1. Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
2. Unsuitable for nephrectomy as judged by treating clinician(s)
3. Not suitable for ‘watch and wait’ policy as determined by treating clinician(s)
4. No prior systemic therapy for renal cell carcinoma
5. Measurable metastatic disease using RECIST v1.1 (see Appendix A)
6. 18 years of age or older
7. Life expectancy of 12 weeks or greater
8. ECOG performance status 0 or 1
9. Adequate organ function as defined by serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to liver metastases; total serum bilirubin ≤1.5 x ULN
10. Adequate haematological function as defined by absolute neutrophil count (ANC) ≥1500/µL, platelets ≥75,000/µL, haemoglobin ≥9.0 g/dL and prothrombin time (PT) ≤1.5 x ULN
11. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min;
12. Urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2g per 24 hours.
13. No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
14. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
15. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including tumour biopsies.
16. Written informed consent

E.4

Principal exclusion criteria

1. The presence of intracranial disease, unless there has been radiological evidence of stable intracranial disease >6 months. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
2. The presence of active second malignancy. Patients will be eligible if they have adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, stable prostate cancer or if treated with curative intent for any other cancer with no evidence of disease for 2 years.
3. Women who are pregnant or are breastfeeding. Female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrolment.
4. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
5. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
6. Gastrointestinal abnormalities including:
a. inability to take oral medication;
b. requirement for intravenous alimentation;
c. prior surgical procedures affecting absorption including total gastric resection;
d. treatment for active peptic ulcer disease in the past 6 months;
e. active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
f. malabsorption syndromes.
7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy).
8. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy).
9. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
10. Active seizure disorder, spinal cord compression, or carcinomatous meningitis.
11. Any of the following within 12 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
12. Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
14. Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

E.5 End points

E.5.1

Primary end point(s)

The proportion of patients treated with axitinib who are free from disease progression 6 months from the commencement of treatment. Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to Response Evaluation Criteria In Solid Tumors (RECIST)v1.1. The main timepoint of interest is 6 months after study entry.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months from start of treatment.

E.5.2

Secondary end point(s)

• Best overall response confirmed according to RECIST v1.1.
• Progression free survival confirmed according to RECIST v1.1.
• Overall survival
• Safety and toxicity of axitinib (by NCI CTC grading version 4).
• Number of patients who become suitable for nephrectomy as a consequence of therapy with axitinib.

All secondary endpoints will be measured from time of registration.

E.5.2.1

Timepoint(s) of evaluation of this end point

Best overall response - during or within 30 days after termination of axitinib
Progression-free survival - first date of either death or confirmed progressive disease - time to last follow-up will be used if patient has not progressed or died and PFS time for the patient will be considered censored.
Overall survival will be measured until the date of death due to any cause - time to last follow-up will be used if patient has not died and survival time for the patient will be considered censored.
Safety and toxicity will be assessed throughout the treatment period.
Number of patients suitable for nephrectomy will be assessed at time of last follow up.

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

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.6.13.1

Other scope of the trial description

Evaluation of changes in biomarkers in response to treatment

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.8.3

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 study end date is deemed to be the date of last data capture.

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