Clinical Trials Register

Summary
EudraCT Number:	2007-003462-18
Sponsor's Protocol Code Number:	AP23573-07-302
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-07-03
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-003462-18

A.3

Full title of the trial

A Pivotal Trial to Determine the Efficacy and Safety of AP23573 when Administered as Maintenance Therapy to Patients with Metastatic Soft-Tissue or Bone Sarcomas

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

AP23573-07-302

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

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	ARIAD PHARMACEUTICALS,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
B.5.2	Functional name of contact point

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/3/05/321 and EU/3/05/312
D.3 Description of the IMP
D.3.1	Product name	Deforolimus
D.3.2	Product code	AP23573
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	deforolimus
D.3.9.1	CAS number	572924-54-0
D.3.9.2	Current sponsor code	AP23573
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	10
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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

Metastatic Soft-Tissue or Bone Sarcomas

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	HLGT
E.1.2	Classification code	10041299
E.1.2	Term	Soft tissue sarcomas

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 compare progression-free survival (PFS) of patients who have achieved complete response, partial response or stable disease following 1st, 2nd or 3rd line chemotherapy when treated with AP23573 versus placebo.

E.2.2

Secondary objectives of the trial

To compare the overall survival (OS) of patients when treated with AP23573 versus placebo
To compare the best target lesion response of patients receiving AP23573 versus placebo
To assess changes in cancer-related symptoms in those patients treated with AP23573 compared to those treated with placebo
To determine the safety and tolerability of AP23573

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

FARMACOGENETICA

E.3

Principal inclusion criteria

1.Documented histologic diagnosis of soft-tissue or bone sarcoma that has metastasized, with the exception of certain histopathologic subtypes of sarcomas recognized by experts to derive no benefit from conventional chemotherapies or with distinctly different natural histories. 2.Ongoing complete response, partial response or stable disease as defined by RECIST guidelines after a minimum of 4 cycles (and maximum of 12 months) of any one of 1st, 2nd or 3rd line of prior cytotoxic chemotherapy for metastatic disease. 3.Disease status (SD or better response) confirmed by a central review of the most recent 2 consecutive radiological evaluations (e.g., CT or MRI scans) obtained a minimum of 6 and a maximum of 10 weeks apart. 4.Patients with partial response or stable disease at study entry must have least one measurable or evaluable lesion as defined by RECIST guidelines (see Attachment D) 5.Patients with metastatic bone sarcoma must have at least one measurable visceral lesion or have achieved a complete response of visceral metastasis. 6.ECOG performance status of 0 or 1 (see Attachment A) 7.Male or female patients ≥ 13 years of age (patients 13-17 years of age must weigh at least 100lbs. (45.4 kg)). In regions where applicable local law prohibits enrollment of patients <18 years of age, only patients ≥18 years of age will be eligible. 8.Patients must have normal organ and marrow function as defined below: leukocytes ≥ 3,000/µL absolute neutrophil count ≥ 1,500/µL platelets ≥ 100,000/µL total bilirubin below institutional upper limit of normal (unless patient has Gilbert’s disease in which case ≤1.5 x ULN) AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal (or ≤ 5 x ULN if liver metastases are present) creatinine ≤1.5 X ULN for the institution (or calculated creatinine clearance ≥ 50 mL/min/1.73 m2) 9.Serum cholesterol ≤ 350 mg/dL and triglycerides ≤ 400 mg/dL 10.Male and female patients who are not surgically sterile or postmenopausal must agree to use reliable methods of birth control from time of screening until 30 days after the last dose of the study drug 11.Able to understand and willing to sign a written informed consent document 12.Completed 1st, 2nd or 3rd line chemotherapy and have received last dose ≥ 3 weeks prior to randomization 13.Randomization and treatment to begin ≤ 8 weeks following previous treatment

E.4

Principal exclusion criteria

1.Women who are pregnant or lactating 2.Presence of known or active brain or CNS metastases 3.Prior therapy with rapamycin or rapamycin analogs, including AP23573 4.Ongoing toxicity associated with prior anticancer therapy ≥ Grade 2 (excluding alopecia) according NCI common terminology criteria 5.Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ) 6.Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin) 7.Concomitant treatment with medications that induce or inhibit CYP3A. Patients should be off these medications ≥ 2 weeks prior to the first dose of AP23573 8.Significant uncontrolled cardiovascular disease 9.Active infection requiring systemic therapy 10.Known HIV infection 11.Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug 12.Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of study drug (with the exception of minor procedures, e.g., central venous access port placement) 13.Presence of any life-threatening illness or organ system dysfunction which, in the option of the Investigator, would either compromise the patient’s safety or interfere with evaluating the safety of the study drug

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS), defined as the time from the date of randomization to the date of documented progressive disease or death (whichever occurs first)

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

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

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)

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.8.3

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.8.6 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

Information not present in EudraCT

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

Information not present in EudraCT

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minori

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

665

F.4.2.2

In the whole clinical trial

705

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

2008-06-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-01-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-12-20

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