Clinical Trials Register

Summary
EudraCT Number:	2008-005074-12
Sponsor's Protocol Code Number:	20070411
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-11-18
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

Spain - AEMPS

A.2

EudraCT number

2008-005074-12

A.3

Full title of the trial

A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination with AMG 479 in Subjects with Advanced, Refractory Solid Tumors.
--------------------------------------------------------
Estudio abierto de fase 1b/2 con escalada de dosis de AMG 655 en combinación con AMG 479 en sujetos con tumores sólidos refractarios y avanzados.

A.4.1

Sponsor's protocol code number

20070411

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	Amgen 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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AMG 655
D.3.2	Product code	AMG 655
D.3.4	Pharmaceutical form	Intravenous 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	AMG 655
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	30
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	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	AMG 479
D.3.2	Product code	AMG 479
D.3.4	Pharmaceutical form	Intravenous 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	AMG 479
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	30
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.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

Part 1: Advanced, treatment-refractory solid tumors
Part 2: Advanced non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer, ovarian cancer, or sarcoma.
------------------------------------------------------------
Parte 1:tumores sólidos refractarios y avanzados.
Parte 2:Cáncer de pulmón no microcítico avanzado (CPNM), cáncer colorrectal (CRC), cáncer pancreático, cáncer de ovario o sarcoma.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10061451
E.1.2	Term	Colorectal cancer

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10033604
E.1.2	Term	Pancreatic cancer

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
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

Part 1: To identify a dose of AMG 655 in combination with AMG 479 that is safe and
tolerated as determined by the incidence of dose limiting toxicity (DLT).
Part 2: To estimate the efficacy, as measured by the objective response rate (ORR;
confirmed complete response [CR] and partial response [PR] using modified Response Evaluation Criteria in Solid Tumors [RECIST]) of AMG 655 in combination with AMG 479.

E.2.2

Secondary objectives of the trial

Part 1:
- To evaluate the safety and tolerability of AMG 655 in combination with AMG 479.
- To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation.
- To evaluate the pharmacokinetics (PK) of AMG 655 and of AMG 479.
Part 2:
- To estimate the efficacy of AMG 655 in combination with AMG 479, as measured by
time to response, duration of response, and progression-free survival (PFS).
- To evaluate the safety and tolerability of AMG 655 in combination with AMG 479.
- To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation.
- To evaluate the PK of AMG 655 and of AMG 479.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Disease Related
- Part 1: Histologically or cytologically confirmed, locally advanced or metastatic,
treatment-refractory solid tumors
- Part 2: Histologically or cytologically confirmed, locally advanced or metastatic
- NSCLC (squamous or non-squamous cell carcinoma; up to 2 prior treatment regimens)
- CRC (up to 2 prior treatment regimens)
- Pancreatic cancer (up to 1 prior treatment regimen)
- Ovarian cancer (up to 2 prior treatment regimens), or
- Sarcoma (up to 2 prior treatment regimens)
- according to cohort availability
- Part 2: Measurable disease according to modified RECIST (at least 1 measurable
lesion)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix G)
- Life expectancy ≥ 3 months
Demographic.
- Women or men ≥ 16 years of age
Ethical
- Before any study-specific procedure, the appropriate written informed consent must
be obtained (Section 12.1)
Laboratory
Within 7 days before enrollment, the following test results must be obtained:
- Hematological function, as follows:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
(without transfusion ≤ 14 days prior to enrollment)
- Renal function, as follows:
- Serum creatinine ≤ 2 x ULN
- Hepatic function, as follows:
- Aspartate aminotransferase (AST; SGOT) ≤ 2.5 x ULN
( 5 x ULN if attributable to liver metastases)
- Alanine aminotransferase (ALT; SGPT) ≤ 2.5 x ULN
(≤ 5 x ULN if attributable to liver metastases)
- Total Bilirubin ≤ 1.5 x ULN
(≤ 3 x ULN for subjects with UGT1A1 promoter polymorphism ie, Gilbert syndrome, confirmed by genotyping or Invader UGT1A1 molecular assay prior to enrollment)
- Coagulation:
- Partial thromboplastin time (PTT) ≤ 1.3 x ULN
- International normalized ratio (INR) ≤ 1.5,
- Amylase ≤ 2 x ULN
- Lipase ≤ 2 x ULN
- Adequate glycemic function, for subjects with known diabetes (Type 1 or 2), as
follows:
- Must be controlled with a glycosylated hemoglobin (HgbA1c) of ≤ 8.0%
- Documented fasting blood sugars ≤ 160 mg/dL. Diabetic subjects who have
recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations ≤ 160 mg/dL may be considered regardless of HgbA1c value, if per investigator discretion they are considered to have adequate glycemic function
- Negative pregnancy test within 3 days prior to enrollment (females of child-bearing potential only)
General
- Plan to begin protocol specific therapy ≤ 7 days after enrollment

E.4

Principal exclusion criteria

Disease Related
- Presence of uncontrolled central nervous system (CNS) disease:
- Subjects with CNS metastases that are both definitively treated and
stably controlled are eligible if all of the following apply:
(1) definitive therapy has been administered (surgery and/or radiation therapy);
(2) there is no additional treatment planned for brain metastases;
(3) the subject is clinically stable; and
(4) the subject is off corticosteroids or on a stable dose of corticosteroids for at
least 14 days prior to enrollment.
- Part 2: Any prior or synchronous other malignancy, except:
- Malignancy treated with curative intent and with no known active disease present
for ≥ 3 years before enrollment and considered to be at low risk for recurrence by
the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
Cancer Therapy
- Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or
approved anticancer proteins/antibodies therapy ≤ 28 days before enrollment,
except:
- In Part 1, patients may continue approved hormonal therapy as medically
indicated
- Unresolved toxicity(ies) from prior anti-cancer therapy, which may increase the risks
associated with study participation
- Prior treatment with death receptor agonists (including but not limited to
rhApo2L/TRAIL [AMG 951], apomab, mapatumumab, lexatumumab, CS-1008)
- Prior treatment with IGF receptor antagonists (including but not limited to
CP-751,871, MK0646, AVE1642 or IMC-A12)
- Patients may not have received prior radiotherapy to > 25% of the bone marrow.
Radiation must have been concluded ≥ 14 days prior to enrollment. Patients must
have recovered from all potential side effects and must be clinically stable.
Medications/ Treatments
- Therapeutic anticoagulation treatment within 7 days prior to enrollment.
- Prophylactic anticoagulation of venous access devices (eg, with low-dose
coumadin [1-2 mg/day] or low-dose heparin) is allowed, provided PTT and INR
eligibility criteria are met.
- Recent infection requiring systemic anti-infective treatment that was completed
- 14 days before enrollment (with the exception of uncomplicated urinary tract
infection or upper respiratory tract infection)
Medical Conditions
- Major surgical procedure ≤ 28 days before enrollment, or not yet recovered from
prior major surgery
- Minor surgical procedure (eg, open biopsy) ≤ 7 days before enrollment, or not yet
recovered from prior minor surgery.
Note: uncomplicated placement of vascular access device, fine needle aspiration,
thoracocentesis or paracentesis ≥ 3 days prior to enrollment is acceptable
- History of bleeding diathesis
- Pulmonary embolism or arterial/venous thromboembolism within 6 months
- Known positive test for human immunodeficiency virus, hepatitis C virus or acute or
chronic hepatitis B infection
- Any clinically significant medical or psychiatric condition, co-morbid disease,
addictive disorder, or laboratory abnormality (eg, cardiovascular disease or chronic
obstructive pulmonary disease), which may increase the risks associated with study
participation or study treatments or could interfere with the safe delivery of study
treatment or increase risk of toxicity
- Subject has any kind of disorder that compromises the ability of the subject to give
written informed consent and/or to comply with study procedures
General
- Subject is currently enrolled in or has not yet completed at least 30 days since
ending other investigational device or drug study(s), or subject is receiving other
investigational agent(s)
- Subject previously enrolled in this study
- Subject of child-bearing potential is evidently pregnant (eg, positive human chorionic
gonadotropin test) or is breast feeding
- Woman or man with partner of childbearing potential not consenting to use adequate
contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm
plus condom), or abstinence during the course of the study and for 3 months after
the last study drug administration for women, and 6 months for men
- Subject has known hypersensitivity to any of the products to be administered during the study
- Subject is not able to tolerate IV drug infusions
- Subject unwilling or unable to comply with study requirements
- Subject will not be available for follow-up assessments

E.5 End points

E.5.1

Primary end point(s)

Part 1: The incidence of adverse events and clinical laboratory abnormalities defined as DLT
Part 2: ORR (confirmed CR and PR, by modified RECIST)

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

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

1b/2

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

Information not present in EudraCT

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

The end of the clinical study will be defined as the date when all subjects have
completed the long-term follow-up period, have withdrawn from study or have died (until a maximum 36 months from the date the last subject was enrolled), whichever is earlier.

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.1.1.1	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)	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	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	5
F.4.2	For a multinational trial
F.4.2.1	In the EEA	22
F.4.2.2	In the whole clinical trial	108

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

2009-03-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-12-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-08-10

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