Clinical Trials Register

Summary
EudraCT Number:	2005-002717-21
Sponsor's Protocol Code Number:	A4021011
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:	2006-07-23
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

2005-002717-21

A.3

Full title of the trial

A PHASE 2, RANDOMIZED, NON-COMPARATIVE, TWO-ARM OPEN LABEL, MULTIPLE-CENTER STUDY OF CP-751,871 IN COMBINATION WITH DOCETAXEL/PREDNISONE IN CHEMOTHERAPY- NAÏVE (ARM A) AND DOCETAXEL/PREDNISONE REFRACTORY (ARM B) PATIENTS WITH HORMONE INSENSITIVE PROSTATE CANCER

A.3.2

Name or abbreviated title of the trial where available

n/a

A.4.1

Sponsor's protocol code number

A4021011

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	Pfizer Inc,235 East 42nd Street, New York,NY 10017
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	CP-751,871
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CP-751,871
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Taxotere
D.2.1.1.2	Name of the Marketing Authorisation holder	Aventis Pharma SA
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	Taxotere
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	docetaxel
D.3.9.1	CAS number	114977-28-5
D.3.9.3	Other descriptive name	Taxotere
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	20
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	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Deltacotril Enteric
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Deltacotril Enteric
D.3.4	Pharmaceutical form	Gastro-resistant 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	prednisone
D.3.9.1	CAS number	53-03-2
D.3.9.3	Other descriptive name	deltacotril
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	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)	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	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

Metastatic hormone refractory (androgen indepedent) progressive prostate cancer (HRPC)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10062904
E.1.2	Term	Hormone-refractory prostate cancer
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 study procedures to be followed after March 31, 2011 are outlined in Appendix M of the protocol.

Primary Objective:
• Arm A: To assess the efficacy, in term of PSA response rate, of multiple doses of CP 751,871 in combination with docetaxel and prednisone in chemotherapy-naïve patients with HRPC.
• Arm B: To assess the efficacy, in terms of PSA response rate, of CP-751,871 in combination with docetaxel/prednisone in patients with HRPC that progress on docetaxel/prednisone alone.

E.2.2

Secondary objectives of the trial

• To assess efficacy in terms of PFS (progression free survival).
• To assess the safety and tolerability of multiple doses of CP-751,871 in combination
with docetaxel and prednisone.
• To assess population PK of CP-751,871 when used in combination with docetaxel
and prednisone.
• To evaluate the effect of CP-751,871 in combination with docetaxel and prednisone
on biomarkers.
• To test for the occurrence of HAHA response to CP-751,871.
• The feasibility of performing quality of life and pain questionnaires in this patient
population will be investigated.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Histologically confirmed adenocarcinoma of the prostate (a new diagnostic biopsy
is not required).
2.Evidence of metastatic disease either on bone or CT scans.
3.At least 18 years old.
4.PSA above 5 ng/mL.
5.Progressive disease after at least 1 hormonal treatment (orchiectomy, estrogens, LHRH therapy etc.) with documented testosterone levels less than 50 ng/dL (equivalent to 1.7 nmol/L) and progressive disease defined by the following:
- An increase in PSA>50% over nadir value on hormonal therapy measured on 3 successive occasions at least 1 week a part. If the third measurement is lower than the second, a fourth measurement will be taken. Only if the fourth measurement is higher than the second, the patient will be enrolled in the study.
- Disease progression as defined by RECIST
- Two or more new bone lesions
6.Concurrent use of LHRH agonist is required if the patient has not been surgically castrated.
7.Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 determined within 2 weeks prior to enrollment (Appendix E).
8.Recovered to CTCAE <Grade 1 or deemed irreversible from the effects of prior cancer therapy. CTCAEs > Grade 1 that are not considered a safety risk by the sponsor and investigator will be allowed.
9.Stable level of pain for at least one week before enrollment.
10.Absolute neutrophil count of >1.5 x 109/L and platelets >100 x 109/L.
11.Adequate blood chemistry parameters as defined by:
- Creatinine <1.7 mg/dL (equivalent to 151 micromol/L). If creatinine is >1.7 mg/dL, the calculated creatinine clearance must be >40 ml/min from the Cockcroft Gault or MDRD formulas (Appendix D).
- Bilirubin <ULN.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <1.5 x ULN
12. Hemoglobin >10 g/dL.
13. Written and voluntary informed consent understood, signed and dated.

E.4

Principal exclusion criteria

1.Prior chemotherapy or radioisotopes treatment for prostate cancer.
2.Prior anti IGF 1R and antibody based investigational therapies. Other investigational therapies (targeted or vaccine), unless otherwise agreed by investigators and sponsor, will require 4 weeks wash out period before enrollment.
3.Antiandrogen therapy (eg, flutamide) for primary cancer within 4 weeks prior to enrollment (6 weeks in the case of bicalutamide, nilutamide or other long acting anti androgens).
4.Radiation therapy to more than 25% of the bone marrow.
5.Local radiation within 2 weeks of enrollment.
6.Surgery within 4 weeks prior to study enrollment or not fully recovered from side effects of previous procedures.
7.Use of products known to affect PSA levels within 4 weeks of enrollment (eg, PC Calm, PC Plus, PC SPES, finasteride).
8.A serious uncontrolled medical disorder or active infection that would impair the ability to receive study treatment.
9.Significant active cardiac disease including: uncontrolled high blood pressure (ie, systolic blood pressure >160 mmHg, diastolic blood pressure >95 mm Hg), unstable angina, deep venous thrombosis, pulmonary embolism, cerebro vascular attack, valvular disease, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias.
10.Subjects who are receiving chronic high dose immunosuppressive steroid therapy. Use of high dose corticosteroids within 2 weeks prior to enrollment (≥100 mg prednisone per day or >40 mg dexamethasone per day). Previous steroid treatment is allowed but must be stopped at enrollment. Low dose steroid use for the control of nausea and vomiting (eg, dexamethasone 20 mg/day for up to 5 days) will be allowed. Topical steroid use is permitted. Inhaled steroids are permitted. Use of dexamethasone as pre medication is not an exclusion criterion.
11. Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80.
12. Medical contraindication to any of the docetaxel pre medications.
13. Neuropathy greater than Grade 1 or evidence of unstable neurological symptoms within 4 weeks prior to enrollment.
14. Brain metastasis. Unevaluated central nervous system (CNS) symptoms suggestive of brain metastases within 2 weeks prior to enrollment. CNS symptoms must be evaluated with a computerized tomography (CT) scan or magnetic resonance imaging (MRI).
15. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
16. Subjects with reproductive potential who are not using adequate barrier methods on treatment.
17. Active malignancy other than prostate cancer within the past five years with the exception of non melanoma skin cancer (basal or squamous-cell skin cancer).
18. Subjects who have been admitted to an institution by virtue of an order issued by either the judicial or administrative authorities.

E.5 End points

E.5.1

Primary end point(s)

PSA Response Rate

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

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

QoL

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

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

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

as per protocol

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.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

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

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

200

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)

All patients receiving CP 751,871 will be followed up for emerging subacute and late toxicity for a period of 150 days from the last dose, unless the patient withdraws consent or receives another treatment for his/her disease. Follow-Up visits should be scheduled once a month.
Additional follow up study visits may be scheduled to monitor unresolved adverse events or efficacy.

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

2006-07-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-05-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-09-20

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