Clinical Trials Register

Summary
EudraCT Number:	2011-000765-12
Sponsor's Protocol Code Number:	MICORYX
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-03-16
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

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2011-000765-12

A.3

Full title of the trial

Phase I/IIa study of immunization with frameshift peptides administered with Montanide ISA-51 VG in patients with advanced MSI-H colorectal cancer

A.3.1

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

vaccination study in patients with advanced MSI-H colorectal cancer

A.4.1

Sponsor's protocol code number

MICORYX

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	Oryx GmbH & Co. KG
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Krankenhaus Nordwest
B.5.2	Functional name of contact point	Institut für Klin.-Onkol. Forschung
B.5.3	Address:
B.5.3.1	Street Address	Steinbacher Hohl 2-26
B.5.3.2	Town/ city	Frankfurt
B.5.3.3	Post code	60488
B.5.3.4	Country	Germany
B.5.4	Telephone number	496976014420

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	Information not present in EudraCT
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	micoryx
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
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)	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	Information not present in EudraCT

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

advanced MSI-H colorectal cancer

E.1.1.1

Medical condition in easily understood language

advanced MSI-H colorectal 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	PT
E.1.2	Classification code	10061451
E.1.2	Term	Colorectal 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

Phase I Part:
Safety of the vaccine

Phase IIa Part:
Immune response against the FSP mix

E.2.2

Secondary objectives of the trial

Phase I Part:
Immune response against the FSP mix
Tumor response

Phase IIa Part:
Safety of the vaccine
Tumor response

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Histologically confirmed, surgically resected colorectal cancer of advanced stage (UICC stage III/UICC stage IV). This comprises patients with lymph node metastases (UICC stage III), metastasis to one distant organ (UICC IV, M1a), to more than one distant organ, or patients with peritoneal carcinosis (M1b)
•Detection of high level microsatellite instability (MSI-H) in the resected tumor sample according to the international consensus criteria (multiplex PCR of quasi-monomorphic microsatellite markers BAT25, BAT26, CAT25), see Appendix 1.
•Prior adjuvant standard therapy (chemotherapy with 5-fluorouracil/folinic acid, oxaliplatin, irinotecan or combinations of these)
OR
Prior palliative standard therapy in the first, second and third line (chemotherapy with 5-fluorouracil, oxaliplatin, irinotecan or combinations of these and/or treatment with anti-EGFR antibodies cetuximab or panitumumab alone or in combination with chemotherapy) with either complete or partial remission, stable disease, or disease progression under therapy;
OR
Patient has refused adjuvant or palliative standard therapy (chemotherapy using 5-fluorouracil, oxaliplatin, or regimens combining these).
•Expected survival of at least six months.
•Full recovery from surgery or radiation therapy
•ECOG performance status 0, 1 or 2.
•The following laboratory results:
Neutrophil count > 1.5 x 109/L
Lymphocyte count > 0.5 x 109/L
Platelet count > 100 x 109/L
Serum bilirubin < 2mg/dL
•Male or female patients ≥ 18 years old
•Last therapy discontinued at least 4 weeks prior to vaccination.
•Patient´s written informed consent for participation in the trial

E.4

Principal exclusion criteria

•Prior treatment with FSPs AIM2(-1), HT001(-1) and TAF1B(-1)
•Clinically significant heart disease (NYHA Class IV).
•Other serious illnesses, eg, serious infections requiring antibiotics or bleeding disorders.
•History of immunodeficiency disease or autoimmune disease.
•Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.
•HBV, HCV or HIV positivity.
•Chemotherapy, any type of radiation therapy, or immunotherapy within 4 weeks before study entry
•Concomitant treatment with steroids, antihistaminic drugs, or nonsteroidal anti-inflammatory drugs (unless used in low doses for prevention of an acute cardiovascular event or for pain control). Topical or inhalational steroids are permitted.
•Participation in any other clinical trial
•Pregnancy or lactation.
•Women of childbearing potential who are not using a medically acceptable means of contraception. Appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap).
•Psychiatric or addictive disorders that may compromise the ability to give informed consent.
•Lack of availability of a patient for immunological and clinical follow-up assessment.
•Brain metastases (symptomatic and non-symptomatic)

E.5 End points

E.5.1

Primary end point(s)

• Safety of the vaccine administration as assessed by the number and severity of adverse events categorized according to CTC criteria version 4.0 and the probability of the induction of immune tolerance. Immune tolerance is defined as a significant and sustained decline of antigen-specific cellular immune responses after vaccination (weeks 9, 17 and 25, or weeks 17 and 25) compared to the antigen-specific cellular immune response measured before vaccination (week 1), as assessed by IFN-gamma ELISpot using assay-specific cut-off values. A minimum observation period of 9 weeks is required for patients that do not complete the entire vaccination schedule. In these patients tolerance is defined as significant decline of cellular immune response in week 9 compared to the immune response in week 1.

E.5.1.1

Timepoint(s) of evaluation of this end point

at every visit

E.5.2

Secondary end point(s)

• Immune response against FSP peptides. A positive immune response is defined as positive DTH response against at least one of the peptides or a humoral (ELISA for the detection of FSP-specific IgG/IgM/IgA) and/or CD8 and/or CD4 cellular (IFN gamma ELISpot for the detection of FSP-specific T cells) immune response exceeding the assay specific cut-off values for a positive response against at least one of the three peptides.
• Tumor response as assessed by CT or MRI scans according to RECIST (applies for stage IV patients only)

E.5.2.1

Timepoint(s) of evaluation of this end point

Immune response: humoral immune response at weeks 1, 3, 9, 11, 17, 19, 25
cellular immune response and DTH: weeks 1, 9, 17, 25.
tumor response: every 8 weeks

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

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

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

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

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

Last visit is the end of the study

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

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.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)

None

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

2011-08-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-08-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-05-30

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