Clinical Trials Register

Summary
EudraCT Number:	2009-009035-30
Sponsor's Protocol Code Number:	CP15-0802
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:	2009-08-21
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

2009-009035-30

A.3

Full title of the trial

Randomized Phase 2 Trial Investigating Liposomal Doxorubicin With or Without Anti Platelet Derived Growth Factor Receptor-Alpha (PDGFRα) Monoclonal Antibody IMC-3G3 in Patients With Platinum-Refractory or Platinum-Resistant Advanced Ovarian Cancer.

A.4.1

Sponsor's protocol code number

CP15-0802

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	ImClone LLC
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.3.1	Product name	IMC-3G3
D.3.2	Product code	IMC-3G3
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	IMC-3G3
D.3.9.3	Other descriptive name	recombinant human monoclonal antibody (Mab) targeted to PDGFRα
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	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	Yes
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	Liposomal doxorubicin
D.3.2	Product code	Liposomal doxorubicin
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.3.8	INN - Proposed INN	Liposomal doxorubicin
D.3.9.1	CAS number	23214-92-8
D.3.9.2	Current sponsor code	Liposomal doxorubicin
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

Platinium-refractory or Platinium-resistant Advanced Ovarian Cancer

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer

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 primary objective of this study is to evaluate the PFS in patients with platinum-refractory or platinum resistant advanced ovarian cancer when treated with the monoclonal antibody IMC-3G3 in combination with liposomal doxorubicin (Arm A) versus liposomal doxorubicin alone (Arm B).

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
· To evaluate the overall survival (OS) in each arm
· To evaluate the ORR in each arm
· To evaluate the median duration of response in each arm
· To evaluate the safety profile in each arm
· To evaluate the pharmacokinetic and immunogenicity profiles of IMC-3G3
· To evaluate the pharmacodynamic profile by assessing:
1. the association between tumor PDGFRα expression (assessed by immunohistochemistry) and clinical outcomes (PFS, ORR, etc)
2. the relationship between IMC-3G3 treatment and plasma vascular endothelial growth factor (VEGF)/PDGF levels
3. the relationship between plasma VEGF/PDGF levels and clinical outcomes
· To provide descriptive safety and efficacy statistics for patients who crossover to
IMC-3G3 monotherapy following progressive disease (PD) on liposomal doxorubicin
monotherapy

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each patient must meet the following criteria to be enrolled in this study:
1. The patient has histologically or cytologically confirmed epithelial ovarian cancer,
primary peritoneal carcinoma, fallopian tube cancer, or ovarian clear cell carcinoma.
2. The patient has completed at least one and up to three platinum-containing regimens (involving cisplatin, carboplatin, or another organoplatinum) for the management of this condition. Treatment may have included intraperitoneal therapy, high-dose therapy, consolidation or extended therapy administered after surgical or
nonsurgical assessment.
3. The patient must have at least one of the following: a platinum-free interval of
≤ 12 months after the final dose of primary or subsequent platinum-based therapy
(platinum-resistant), progression during primary or subsequent platinum-based therapy (platinum-refractory), or persistent radiographic disease after primary or subsequent platinum-based therapy (platinum-refractory).
4. The patient has at least one unidimensionally measurable target lesion (≥ 20 mm with conventional techniques, or ≥ 10 mm by spiral computed tomography [CT] or magnetic resonance imaging [MRI]), as defined by Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v 1.0) guidelines.
5. The patient is of age ≥ 18 years.
6. The patient has recovered to Grade ≤ 1 by the National Cancer Institute Common
Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other
targeted therapies for ovarian cancer, with the exception of alopecia or peripheral
neuropathy (which must have resolved to Grade ≤ 2). The exceptions for such effects are
allowed lab values of ≤ Grade 2 specified elsewhere in these inclusion criteria. (For
example, criterion # 9 states that a patient with hemoglobin ≥ 9.5 g/dL is considered
eligible, even though NCI-CTCAE v 3.0 defines this value as Grade 2 decreased
hemoglobin.
7. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at study entry.
8. The patient has the ability to understand and the willingness to sign a written informed consent.
9. The patient has adequate hematological functions (absolute neutrophil count [ANC] ≥ 1200 cells/μL, hemoglobin ≥ 9 g/dL, and platelets ≥ 100,000 cells/μL).
10. The patient has adequate hepatic function as defined by total bilirubin ≤ 1.5 × the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × the ULN (or ≤ 5 × the ULN in the presence of known liver metastases).
11. The patient has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the patient’s creatinine clearance is ≥ 60 mL/min.
12. The patient has urinary protein ≤ 1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate
< 1000 mg of protein to allow participation.
13. The patient must have adequate coagulation function as defined by International
Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN. Patients on anticoagulation must be on a stable dose of anticoagulant with a therapeutic INR and no active bleeding within 14 days prior to randomization, or on low molecular weight heparin AND have no pathological condition carrying a high risk of bleeding. Mild elevations of PTT of up to 1.5 × the ULN are acceptable, provided that,
in the opinion of the investigator, they are related to ongoing use of coumarins (eg,
warfarin).
14. The patient has a pre-study echocardiogram or multigated acquisition (MUGA) scan with an actual left ventricular ejection fraction (LVEF) ≥ 50%, within 21 days prior to randomization.
15. Because the teratogenicity of IMC-3G3 is not known, women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization and for the duration of study participation.

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will be excluded from the study:
1. The patient has brain metastases or leptomeningeal disease.
2. The patient received more than one biologic and/or more than one hormonal therapy, administered either concomitantly with platinum-based therapy or separately.
3. The patient has a history of treatment with other agents targeting PDGF or PDGFR.
4. The patient has an increased level of CA-125 in the absence of concomitant clinical or radiographic progression.
5. The patient has received radiotherapy, chemotherapy, or biologic therapy directed at the malignant tumor within 3 weeks prior to randomization, or hormonal therapy directed at the malignant tumor within 1 week prior to randomization. Continuation of hormone replacement therapy is permitted.
6. The patient has a suspected impending bowel obstruction (including partial obstruction), based on clinical or radiographic data.
7. The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-3G3.
8. The patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study
requirements.
9. The patient has a history of another primary cancer, with the exception of:
a) curatively resected nonmelanomatous skin cancer;
b) curatively treated cervical carcinoma in-situ; or
c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years prior to randomization.
10. The patient is pregnant or lactating.
11. The patient has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days prior to randomization. The exceptions for such effects are allowed lab values and toxicities of ≤ Grade 2, specified in the inclusion criteria. (For example, inclusion criterion # 9 states that a patient with hemoglobin ≥ 9.5 g/dL is considered eligible, even though NCI-CTCAE v 3.0 defines this value as Grade 2 decreased hemoglobin).
12. The patient has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to randomization.
13. The patient has participated in clinical trials of experimental agents within 28 days prior to randomization.
14. The patient has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
15. The patient has a serious or nonhealing active wound, ulcer, or bone fracture.
16. The patient has known human immunodeficiency virus positivity.
17. The patient had a major surgical procedure, an open biopsy, or significant traumatic injury 28 days prior to randomization.
18. The patient has received an anthracycline for any indication in the past.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint for this study is progression free survival. PFS is defined as the time from the day of randomization to the first evidence of progression as defined by RECIST (V1.0) guidelines or death from any cause.

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

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

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Patients (Arm A and B) may be placed on IMC-3G3 monotherapy (safety/efficacy)

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

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

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	30
F.4.2	For a multinational trial
F.4.2.1	In the EEA	55
F.4.2.2	In the whole clinical trial	110

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

2009-09-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-10-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-05-28

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