Clinical Trials Register

Summary
EudraCT Number:	2011-000729-55
Sponsor's Protocol Code Number:	8669-056
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:	2011-10-07
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

2011-000729-55

A.3

Full title of the trial

A Phase I Study of Ridaforolimus in Paediatric Patients with Advanced Solid Tumours

A.3.1

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

Oral MK8669 in Children/Adolescents with Solid Tumors (6-17 years)

A.3.2

Name or abbreviated title of the trial where available

Oral MK8669 in Children/Adolescents with Solid Tumours(6 - <18years)

A.4.1

Sponsor's protocol code number

8669-056

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/002/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
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	MSD
B.5.2	Functional name of contact point	GCTO UK & Ireland
B.5.3	Address:
B.5.3.1	Street Address	Hertford Road
B.5.3.2	Town/ city	Hoddesdon
B.5.3.3	Post code	EN11 9BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0131 4469844
B.5.5	Fax number	01992 705241
B.5.6	E-mail	philomena_bryans@merck.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/312
D.3 Description of the IMP
D.3.1	Product name	ridaforolimus
D.3.2	Product code	MK-8669
D.3.4	Pharmaceutical form	Gastro-resistant 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	ridaforolimus
D.3.9.1	CAS number	572924-54-0
D.3.9.2	Current sponsor code	MK-8669
D.3.9.3	Other descriptive name	AP23573, rapa-p-ester, deforolimus (former USAN)
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	11 to 33
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

advanced solid tumours including lymphoma and tumours of the central nervous system

E.1.1.1

Medical condition in easily understood language

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10065143
E.1.2	Term	Malignant solid tumour
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To identify the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of ridaforolimus when administered to children from 6 to less than 18 years of age with advanced solid tumours. • To characterize the pharmacokinetics(levels of study drug in the blood) of ridaforolimus when administered to children from 6 to less than 18 years of age with advanced solid tumours.

E.2.2

Secondary objectives of the trial

• To assess for anti-tumour activity of ridaforolimus using RECIST criteria 1.1. • To estimate change from baseline phospho-AKT (pAKT) in platelet rich plasma (blood) after ridaforolimus monotherapy dosing. pAKT is a protein (biomarker) for the PI3K (phosphatidylinositol3 kinase) pathway that plays a role in multiple cellular processes. Biomarkers are used as an indicator of a biological state, they are measured in blood and the concentration reflects the severity or presence of a disease. Also an exploratory objective of the study will be to assess for anti-tumour activity of ridaforolimus and to identify pre-treatment gene expression profiles as predictive biomarkers.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female age 6 to less than 18 years on day of signing informed consent. • Histologic or cytologic diagnosis of a malignant solid tumour, including tumours of the central nervous system and lymphoma that have progressed despite standard therapy or for which no effective standard therapy is known. Patients who have received standard therapy and continue to have biopsy proven residual stable disease are eligible. In the absence of a biopsy, patients with sarcoma would be eligible on the basis of persistent PET activity or by MIBG in neuroblastoma. • Patients may have measurable (per RECIST 1.1) or non-measurable disease. • Patient must be able to swallow tablets. • Performance Status: Lansky Play Scale ≥70 for children <10 years of age; Karnofsky score ≥70 for children ≥10 to <16 years; or ECOG Status 0-2 for patients age 16 and older. • Patient has a Body Surface Area (BSA) that allows evaluation of the current dose level.

E.4

Principal exclusion criteria

• Patients currently receiving any other investigational agents or using any investigational devices. • Patients with leukaemia. • Patients who have previously received ridaforolimus, rapamycin, or other rapamycin analogs. • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ridaforolimus. • Patient has persistent acute toxicity from previous therapy ≥ Grade 2 by NCI CTCAE Version 4 (excluding alopecia, neuropathy, or hearing loss). • Uncontrolled intercurrent illness despite adequate therapy. • Pregnancy or females who are breastfeeding. • Patient has a requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A). Patients should be off these medications for at least 2 weeks prior to the first dose of ridaforolimus. • Patient has poorly controlled Type 1 or 2 diabetes, defined as a fasting glucose >160 mg/dL.

E.5 End points

E.5.1

Primary end point(s)

• Safety endpoint: DLT rate • Pharmacokinetics: Mean Day-5 log AUC 0-24 for ridaforolimus

E.5.1.1

Timepoint(s) of evaluation of this end point

• First 21 days of treatment for safety endpoint • First days 1-5 for PK endpoint

E.5.2

Secondary end point(s)

• Response rate defined as the proportion of patients whose best response is PR or CR (per RECIST 1.1). • Summary of change in pAKT

E.5.2.1

Timepoint(s) of evaluation of this end point

• For the duration of study (until discontinuation) for efficacy • For the duration of study (until discontinuation) for pAKT

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

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)

Yes

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)

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.8.5.1

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

France

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

Last subject last visit (LSLV).

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

Yes

F.1.1