Clinical Trials Register

Summary
EudraCT Number:	2011-005219-98
Sponsor's Protocol Code Number:	PH3-01
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-03
Trial 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2011-005219-98

A.3

Full title of the trial

Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax™ Treatment (PRESENT)

A.3.1

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

Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax™ Treatment (PRESENT)

A.3.2

Name or abbreviated title of the trial where available

PRESENT

A.4.1

Sponsor's protocol code number

PH3-01

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01479244

A.5.4

Other Identifiers

Name:

BB-IND

Number:

9187

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Galena Biopharma, 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	Galena Biopharma, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Galena Biopharma, Inc
B.5.2	Functional name of contact point	CMO
B.5.3	Address:
B.5.3.1	Street Address	2000 Crow Canyon Place, Suite 380
B.5.3.2	Town/ city	San Ramon
B.5.3.3	Post code	CA 94583
B.5.3.4	Country	United States
B.5.4	Telephone number	001617969 3167
B.5.5	Fax number	001617244 7645
B.5.6	E-mail	bhamilton@galenabiopharma.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NeuVax TM
D.3.2	Product code	E75, Nelipepimut-S
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Nelipepimut-S
D.3.9.1	CAS number	160212-35-1
D.3.9.2	Current sponsor code	E75
D.3.9.3	Other descriptive name	HER2 P369-377
D.3.9.4	EV Substance Code	SUB33339
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	1.5
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)	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.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.2.1.1.1	Trade name	Leukine
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Corporation (now Sanofi-Aventis)
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Sargramostim
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SARGRAMOSTIM
D.3.9.1	CAS number	123774-72-1
D.3.9.2	Current sponsor code	Leukine
D.3.9.3	Other descriptive name	Recombinant human granulocyte macrophage colony stimulating factor (yeast) rhGM-CSF
D.3.9.4	EV Substance Code	SUB10450MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
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)	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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intradermal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Operable early-stage, node-positive breast cancer

E.1.1.1

Medical condition in easily understood language

Operable early-stage, node-positive breast 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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10071113
E.1.2	Term	Node-positive breast cancer
E.1.2	System Organ Class	100000004864

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 is to compare the disease-free survival (DFS) in subjects with early-stage, operable node-positive breast cancer with low and intermediate HER2 expression who receive standard of care multimodality therapy plus NeuVax or a group receiving equivalent standard of care plus the vaccine adjuvant rhGM-CSF as the control.

E.2.2

Secondary objectives of the trial

5- and 10-year DFS
3-year Overall survival (OS)
5- and 10-year OS
Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)
Overall safety profile and adverse events (AEs)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Qual 1
1. Women, at least 18 years of age
2. Pathological diagnosis of invasive breast adenocarcinoma
3. Breast cancer completely excised, or patient receiving neoadjuvant therapy prior to surgery.
4. One of:
-Total mastectomy and axillary staging with sentinel lymph node dissection or axillary dissection level I/II. Patients with a +ve sentinel lymph node must have undergone completion axillary dissection level I/II.
-BCS (lumpectomy) and axillary staging with sentinel lymph node dissection or axillary dissection level I/II. Patients with a +ve sentinel lymph node must have undergone a completion axillary dissection level I/II unless they had clinically node negative T1-T2 tumors and fewer than 3 involved lymph nodes.
5. Node-positive disease defined as:
-Clinically node +ve disease in patients who present with a suspicious lymph node on physical examination or identified by radiologic imaging that is confirmed histologically by core biopsy or cytologically by fine needle aspiration biopsy. These patients will qualify even if final
pathological assessment of their lymph nodes is -ve (pN0) following neoadjuvant chemotherapy.
- Pathologic pN1 (including pN1mi) or pN2 disease for patients undergoing surgery as initial intervention.
6. Primary tumor stage T1-3 at time of initial breast cancer diagnosis.
Ipsilateral nodes must be N0-1 by clinical evaluation and pN1 M0 or pN2
M0
7. HER2 Tumor tissue status to be confirmed in a Central Lab using IHC
tests Bond™ Oracle™ HER2 IHC System III, Leica Biosystems) or the
same FISH test (PathVysion™ HER2 DNA Probe Kit, Abbott Diagnostics):
•HER2 expression levels as 1+ or 2+ determined by IHC via Bond™
Oracle™ HER2 IHC System III (Leica Biosystems)
•HER2 IHC 2+ intensity gene amplification confirmed by Abbott FISH
PathVysion HER2 DNA Probe Kit determining the HER2 gene count and
HER2 gene/ CEP17 ratio of 2. 0 or less (according to FISH PathVysion
Package Insert).
8. Hormone receptor (ER/PR) status determined by qualified laboratory.
9.Must complete approved regimen of neoadjuvant or adjuvant chemotherapy, or both, consisting of at least 4 cycles before receiving
study treatment (and subjects must have recovered (toxicity recovered
to ≤ Grade 1) from effect of recent surgery, radiotherapy, or adjuvant
chemotherapy as determined by the principal investigator).
10. No more than 12 weeks and no sooner than 1 month from completion
of last SOC therapy, (surgery, adjuvant chemo- or radiotherapy), at time of first study treatment and with no evidence of disease (NED)
11.Must complete approved radiation therapy for subjects with total mastectomy prior to receiving study treatment:
•1-3 +ve axillary nodes – irradiation to chest wall, infraclavicular and
supraclavicular areas and internal mammary nodes not mandatory (may
be administered at discretion of the treating radiation oncologist).
•≥ 4 <10 +ve axillary nodes – chest wall irradiation and irridiation to infraclavicular and supraclavicular area mandatory; Irradiation to axillary area and internal mammary nodes not mandatory.
12.Must complete approved radiation therapy for subjects with BCS prior
to receiving study treatment: Adjuvant breast radiation indicated for all subjects treated with breast conservation (whole breast irradiation with/without "boost" dose of radiation to tumor bed):
•1 to 3 +ve axillary nodes: irradiation to the supraclavicular area, axillary area or internal mammary nodes not mandatory.
•≥ 4 <10 +ve axillary: irradiation to the infraclavicular and supraclavicular areas mandatory; irradiation to the axillary area and internal mammary nodes not mandatory.
13. Subjects with hormone-receptor–positive disease must have adjuvant endocrine therapy after chemotherapy (unless contraindicated).
14.All subjects' willingness for partner use of condom while on study
treatment and 90 days after last dose of study drug. Additionally, if able
to conceive, must agree to double barrier birth control, (spermicidal
foam, gel, etc) in addition to partner use of condom
15.Subject or legal representative able to understand the study objectives and procedures and willing to show consent by signing the informed consent documents.

Qual2:
1.Met all inclusion criteria for HLA typing.
2.HLA-A2 or HLA-A3 haplotype as determined by a third party central lab.
3.Normal CBC with differential.
4.Clinical chemistry <2x normal upper limit of normal range.
5.Adequate kidney and liver function as measured by creatinine, bilirubin, and liver enzymes.
6.ECHO or MUGA scan with cardiac LVEF >50%, or within normal range
for institution, and less than 10% decrease from baseline (post-adjuvant chemo, if available).
7.HER2 expression status determined to be IHC 1+or 2+ in Central Lab with Bond™ Oracle™ HER2 IHC System-III (Leica Biosystems). If HER2 status is 2+, amplified, confirmed in qualified Central lab by Abbott FISH test, PathVysion™ HER2 DNA Probe Kit (ratio of 2. 0 or less).

E.4

Principal exclusion criteria

1. Under 18 years of age.
2. Bilateral breast malignancy.
3. Inflammatory breast cancer.
4. Unconfirmed, nonmalignant but suspicious mass in opposite breast.
5. Primary tumor stage T4.
6. Nodes: clinical N2 or N3 or pathologic /cytologic N3.
7. History of prior breast cancer.
8. History of prior ductal carcinoma in situ (DCIS). Prior lobular carcinoma in situ (LCIS) is allowed.
9. Prior trastuzumab therapy.
10. Ongoing endocrine therapy except for adjuvant hormone therapy for breast cancer; tamoxifen and aromatase inhibitors (i.e., anastrozole, exemestane and letrozole) or LHRH agonists (i.e., goselerlin, leuprolide).
11. New York Heart Association Stage 3 or 4 cardiac disease
12. Pregnant, plan to become pregnant during study treatment duration or breastfeeding.
13. Sensory/motor neuropathy ≥ Grade 2.
14. Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus or any other autoimmune disease that, in the opinion of the investigator, would compromise the subject's safety.
15. Immune deficiency diseases such as immunoglobulin deficiency or immunosuppressive therapy that might interfere with appropriate immune response
16. Positive test for human immunodeficiency virus (HIV), or hepatitis BsAg or hepatitis C
17. Patients on chronic steroid therapy or other immunosuppressive therapy except for topical steroids.
18. Patients with a known hypersensitivity to GM-CSF, yeast-derived products, or any component of the GM-CSF product (e.g. mannitol).
19. Concurrent treatment with other investigational agent.
20. Nonbreast malignancy within 5 years before randomization, except cured superficial recurrent bladder cancer, carcinoma in situ of the cervix (Stage 0 – 1), and basal cell or squamous cell carcinoma of the
skin.
21. Nonmalignant systemic disease that, in the opinion of the investigator, should preclude the subject's participation in the study.

E.5 End points

E.5.1

Primary end point(s)

Disease-Free Survival (DFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

100% (n=141) events, or 36 months whichever is longer.

E.5.2

Secondary end point(s)

5- and 10-year DFS
3-year OS
5- and 10-year OS
Patterns of recurrence to include :
-Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)
Safety

E.5.2.1

Timepoint(s) of evaluation of this end point

Upon reaching 100% (n=141) of the required OS events, or after 60 months of follow-up following enrollment of the last subject, whichever is greater.

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

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)

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

Yes

E.8.2.3.1

Comparator description

Control arm = Leukine + Placebo

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

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

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

Bulgaria

Canada

Czech Republic

France

Germany

Hungary

Israel

Korea, Republic of

Poland

Romania

Russian Federation

Ukraine

United Kingdom

United States

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

Last visit of the last subject.

The primary endpoint is disease-Free survival and subjects will be followed for up to 10 years. Treatment will be administered monthly for 6 doses, then every 6 months for 5 doses for a total of 11 doses given over a period of 36 months. Subjects will be followed for up to 10 years.

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.1.2.1

Number of subjects for this age range:

500

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

209

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

Yes

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

490

F.4.2.2

In the whole clinical trial

709

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)

Normal standard of care

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

2013-01-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-08-08

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials