Clinical Trials Register

Summary
EudraCT Number:	2011-000847-25
Sponsor's Protocol Code Number:	EMR63325-013
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-22
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

Netherlands - Competent Authority

A.2

EudraCT number

2011-000847-25

A.3

Full title of the trial

A multi-center, randomized, open-label, mechanism of action trial on the biological effects of the therapeutic cancer vaccine Stimuvax® (L-BLP25) in rectal cancer subjects undergoing neoadjuvant chemoradiotherapy.
Stimuvax® (L-BLP25) in rectal cancer in neoadjuvant chemoradiotherapy (SPRINT)

A.3.1

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

A clinical trial to evaluate the mechanism of action and the safety of the cancer vaccine L-BLP25 in rectal cancer subjects undergoing treatment with chemotherapy and radiotherapy

A.3.2

Name or abbreviated title of the trial where available

SPRINT

A.4.1

Sponsor's protocol code number

EMR63325-013

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	Merck KGaA
B.1.3.4	Country	Germany
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	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck KGaA
B.5.2	Functional name of contact point	Communication Centre Merck KGaA
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Strasse 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.6	E-mail	service@merck.de

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	L-BLP25 (Stimuvax ®)
D.3.2	Product code	EMD531444
D.3.4	Pharmaceutical form	Powder for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	L-BLP25 reconstituted
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	23.395
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)	Yes
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	Endoxana Injection 1g
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter Health Care Ltd.
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	Endoxana Injection 1g
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
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	Cyclophosphamide
D.3.9.1	CAS number	50-18-0
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	1000
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.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

Rectal cancer subjects undergoing neoadjuvant
chemoradiotherapy

E.1.1.1

Medical condition in easily understood language

Rectal 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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10038043
E.1.2	Term	Rectal cancer Duke's C
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 objective of this mechanistic study is to determine the impact of LBLP25
vaccine on the mucinous glycoprotein 1 - (MUC1) specific immune
response in patients with newly diagnosed rectal cancer who are eligible
for neoadjuvant therapy.
L-BLP25 is designed to induce an immune response that may lead to
immune rejection of tumor tissues that aberrantly express MUC1
antigen. MUC1 is highly expressed in all colorectal cancers and since the
adaptive immune system plays a role in the prognosis of rectal cancer, it
is reasonable to speculate that the vaccination with L BLP25 might boost
the tumor-specific immune response and increase the number of TILs.

E.2.2

Secondary objectives of the trial

Immunological changes in tumor microenvironment and in the blood:
phenotypic and functional characterization of effector cells such as T, B, NKT, NK cells, myeloid and plasmacytoid dendritic cells, Tregs, myeloid-derived suppressor cells.

MHC class-I tetramer staining to detect MUC1- and CEA-specific T cells

If immunological changes in tumor microenvironment are related to those observed in peripheral blood.

Differences in skin delayed-type hypersensitivity (DTH) response between subjects treated with L-BLP25 with CPA and subjects treated with L-BLP25 without CPA and subjects receiving neither L-BLP25 nor CPA.

Association between immune responses found in tumor, in blood tests, and in DTH response.

If immune responses found in tumor, in blood, or in skin test vary depending on level of MUC1 expression.

If CEA ELISpot and CEA detection in blood are related.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male and female subjects with histologically documented resectable
rectal adenocarcinoma in stage II-IV.
2.Availability of tumor biopsy sufficient for immunological analysis.
3.Indication to receive neoadjuvant concomitant chemoradiotherapy
consisting of a radiation dose of 45-52 Gy and capecitabine 825 mg/m²
orally twice daily. The use of an equivalent schedule based on 5-
fluorouracil (5-FU) is acceptable.
4.Imaging not older than 4 weeks to document absence of metastatic
disease.
5.Eastern Cooperative Oncology Group (ECOG) performance 5. status of 0 or 1.
6.Written informed consent.
7.18 years of age.

E.4

Principal exclusion criteria

1. Previous chemotherapy and/or previous radiotherapy
of the pelvic region.
2. Relapsing disease.
3. Previous vaccination with any MUC1 vaccine and
other therapeutic cancer vaccines.
4. Previous organ transplantation (bone marrow or solid
organs).
5. Subjects with metastatic disease (except for solitary,
resectable liver or lung metastases). When appropriate,
resection of the solitary liver or lung metastases cannot
be performed during trial treatment but should be
performed either before or after trial treatment.
6. Inadequate hematological function (i.e. platelet count
< 140 x 109/L, or WBC < 2.5 x 109/L, or hemoglobin
< 90 g/L).
7. Clinically significant hepatic dysfunction (i.e. alanine
aminotransferase [ALT] > 2.5 times upper limit of
normal [ULN], or aspartate aminotransferase [AST] >
2.5 x ULN, or bilirubin ≥ 1.5 x ULN).
8. Inadequate renal function (i.e. serum creatinine ≥
1.5 x ULN).
9. Autoimmune diseases.
10. A recognized immunodeficiency disease including
cellular immunodeficiencies, hypogammaglobulinemia
or dysgammaglobulinemia; subjects who have
hereditary or congenital immunodeficiencies.
11. Clinically significant cardiac disease, e.g. New York
Heart Association classes III-IV; uncontrolled angina,
uncontrolled arrhythmia or uncontrolled hypertension,
myocardial infarction in the previous 6 months as
confirmed by medical history and an
electrocardiogram (ECG).

E.5 End points

E.5.1

Primary end point(s)

•Change from baseline of tumor-infiltrating lymphocytes (TILs)
evaluated by immunohistochemical analysis [ Time Frame: 4 months ] [
Designated as safety issue: No ]
•Change from baseline in the Enzyme-linked Immunosorbent Spot
(ELISPOT) Level of Mucin-1 (MUC1) -specific T cells
•Change from baseline in the Enzyme-linked Immunosorbent Spot
(ELISPOT) Level of Carcinoembryonic antigen (CEA)-specific T cells

E.5.1.1

Timepoint(s) of evaluation of this end point

Analysis of primary endpoint will take place after all patients completed the study and database was locked.
For the safety monitoring committee there will be interim safety analyses during the study.

E.5.2

Secondary end point(s)

•Immunological changes from baseline in the tumor microenvironment [
Time Frame: 4 months ] [ Designated as safety issue: No ]
•Immunological changes compared to baseline in peripheral blood [
Time Frame: 4 months ] [ Designated as safety issue: No ]
•Immunological Response to Treatment in Relation to Microsatellite
Instability (MSI) Status [ Time Frame: 4 months ] [ Designated as safety
issue: No ]

E.5.2.1

Timepoint(s) of evaluation of this end point

Analysis of secondary endpoints will take place after all patients completed the study and database was locked.
For the safety monitoring committee there will be interim safety analyses during the study.

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Mode of Action

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

standard radiochemotherapy and surgery only (Arm C)

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

If the trial is not terminated for a reason given in Section 5.6 of the protocol, the trial is finished when the last evaluable subject has the Follow-up / End-of-Trial visit, about 4 months after randomization.

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Subjects will continue to receive medical care according to local standards by their local physician after the end of the trial.

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

2011-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-22

P. End of Trial
P.	End of Trial Status	Completed

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