Clinical Trials Register

Summary
EudraCT Number:	2014-001858-41
Sponsor's Protocol Code Number:	D5082C00002
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:	2014-12-30
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

2014-001858-41

A.3

Full title of the trial

A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)

A.3.1

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

This is a study designed to evaluate the effectiveness and safety of AZD6094 in patients with Papillary Renal Cell Cancer.

A.3.2

Name or abbreviated title of the trial where available

A Phase II Trial to Evaluate the Efficacy of AZD6094 in Patients With PRCC

A.4.1

Sponsor's protocol code number

D5082C00002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02127710

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	Astra Zeneca AB
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	Astra Zeneca AB
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	AstraZeneca AB
B.5.2	Functional name of contact point	Clinical Trial Transparency
B.5.3	Address:
B.5.3.1	Street Address	AstraZeneca, Poland Sp. z o. o., ul. Woloska 5
B.5.3.2	Town/ city	Warsaw
B.5.3.3	Post code	02-676
B.5.3.4	Country	Poland
B.5.6	E-mail	ClinicalTrialTransparency@astrazeneca.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	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.3.2	Product code	AZD6094, HMPL-504
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	Savolitinib
D.3.9.1	CAS number	1313725-88-0
D.3.9.2	Current sponsor code	AZD6094, HMPL-504
D.3.9.3	Other descriptive name	Volitinib (Chinese approved name)
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	100
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.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	AZD6094, HMPL-504
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	Savolitinib
D.3.9.1	CAS number	1313725-88-0
D.3.9.2	Current sponsor code	AZD6094, HMPL-504
D.3.9.3	Other descriptive name	Volitinib (Chinese approved name)
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Papillary Renal Cell Carcinoma (PRCC)

E.1.1.1

Medical condition in easily understood language

Renal Cell Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess the anti-tumour activity of AZD6094 in patients with papillary renal cell carcinoma (PRCC) and in the subgroup of Met-positive patients as measured by investigator-assessment of overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

E.2.2

Secondary objectives of the trial

Assess progression free survival. Assess the safety and tolerability of AZD 6094. Safety profiles will be assessed in terms of AEs and laboratory data, vital signs and ECGs that will be collected for all patients. Pharmacokinetics (PK) of AZD6094 and major metabolites M2 and M3 for AUC, AUC(0-24), AUC(0-t), AUCss, Cmax, Css max, and Css min. Characterise the pharmacokinetics (PK) of AZD6094 and the major metabolites M2 and M3 following administration to steady state after multiple dosing when given orally. Assess change in target lesion tumor size from baseline. Change in Target Lesion is percentage change from baseline in tumor size at 12 weeks. Assess duration of response according to RECIST v1.1. Assess duration of overall survival according to RECIST v1.1. All secondary efficacy measurements will include analyses done in Met-positive patient population.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria
•Provision of informed consent prior to any study specific procedures, sampling and analyses.
•Histologically confirmed papillary renal cell cancer, which is locally advanced
•Availability of an archival tumor sample or a pre-treatment fresh tumor sample for confirmation of PRCC by a central laboratory and other biomarker
•Treatment naive or who have failed on treatment for PRCC.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
•At least one lesion, not previously irradiated, and not chosen for a biopsy if performed during the screening period that can be accurately measured at baseline and which is suitable for accurate repeated measurements.
•Adequate hematological function defined as:
a.(ANC) ≥1500/μL
b.(Hgb) ≥9 g/dL
c.Platelets ≥100,000/μL
•Adequate liver function defined as:
a.(ALT) and (AST) ≤2.5 xthe upper limit of normal (ULN)
b.Total bilirubin ≤1.5 x ULN
•Adequate renal function defined as glomerular filtration rate (GFR) ≥ 30 mL/min,
•Adequate coagulation parameters, defined as International Normalisation Ratio(INR) <1.5 x ULN or activated partial thromboplastin time (aPTT) <1.5 x ULN.
•Patients with known tumor thrombus or deep vein thrombosis (DVT) are eligible if stable on low molecular weight heparin (LMWH) for ≥2 weeks.
•Females should be using adequate contraceptive measures should notbe breast feeding, and must have a negative pregnancy test prior to start of dosing ifof childbearing potential or must have evidence of non-childbearing potential
•Male patients should be willing to use barrier contraception, i.e. condoms, during the study and for 6 months following discontinuation of study drug.
•Ability to swallow and retain oral medications.
•Predicted life expectancy ≥12 weeks.
•Aged at least 18 years.
•Willingness and ability to comply with study and follow-up procedures.
•Ability to understand the nature of this study and give written informed consent.

E.4

Principal exclusion criteria

Exclusion criteria
•Most recent chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents <21 days of the first dose of study treatment. Most recent targeted therapy <14 days of the first dose of study treatment.
•Unresolved toxicities from any prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia.
•Prior or current treatment with a cMet inhibitor (e.g. Foretinib, Crizotinib, Cabozantinib, Onartuzumab). Patients with limited exposure may be discussed with the study medical monitor.
•Strong inducers or inhibitors of CYP3A4, strong inhibitors of CYP1A2, or CYP3A4 substrates with a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John’s Wort)
Known hypersensitivity to the active or inactive excipients of AZD 6094.
•Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy
•Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
•Previously untreated brain metastases.
•Current leptomeningeal metastases or spinal cord compression due to disease.
•Acute or chronic liver or pancreatic disease.
•Uncontrolled diabetes mellitus.
•Gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy
•Any of the following cardiac diseases currently or within the last 6 months:
a.Unstable angina pectoris
b.Congestive heart failure (New York Heart Association [NYHA] ≥ Grade 2
c.Acute myocardial infarction
d.Stroke or transient ischemic attack
•Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >160 mmHg or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment).
•Mean resting correct QT interval (QTc) >470 msec obtained from triplicate ECGs.
•Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms (ECGs), e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec.
•Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital or familial long QT syndrome or family history of unexplained sudden death under 40 years of age or any concomitant medications known to prolong QT interval.
•Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin (LMWH) is allowed.
•Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
•Known diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
•Presence of other active cancers, or history of treatment for invasive cancer ≤5years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
•Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

E.5 End points

E.5.1

Primary end point(s)

Objective tumour response (confirmed PR or CR) as assessed by RECIST v1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Week 12

E.5.2

Secondary end point(s)

•Week 12 and best percentage change from baseline in target lesion tumour size.
•Time-to-event endpoints: e.g., PFS, DoR and OS.
•PK parameters including AUC, Cmax, Tmax, Vz/F, CL/F, t½z, and MRT.
•PDc assessments – total cMet-and phosphorylated-cMet.
•Safety and tolerability (as adverse events are characterised and graded by National Cancer Institute Common Terminology Criteria for Adverse Event [NCI CTCAE] v4.03).

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to Week 12

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Information not present in EudraCT

E.8.1.2

Open

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Canada

Spain

United Kingdom

United States

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

LVLS

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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)

Subjects randomized to AZD6094 may continue to receive AZD6094 as long as they are continuing to show clinical benefit, as judged by the investigator, and in the absence of discontinuation criteria.

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

2015-02-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-04-20

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