Clinical Trials Register

Summary
EudraCT Number:	2012-003741-15
Sponsor's Protocol Code Number:	MSC_apceth_101/1
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:	2013-05-22
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

2012-003741-15

A.3

Full title of the trial

Treatment of Advanced Gastrointestinal Cancer in a Phase I/II trial with modified autologous MSC_apceth_101.
Open-label, multicentre, phase I/II.

Behandlung von fortgeschrittenen Tumoren des Gastrointestinaltraktes in einer Phase I/II Studie mit modifizierten autologen MSC_apceth_101.
Offen, multizentrische Phase I/II.

A.3.1

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

Treatment of Advanced Gastrointestinal Cancer in a Phase I/II trial with modified autologous MSC_apceth_101

Behandlung von fortgeschrittenen Tumoren des Gastrointestinaltraktes in einer Phase I/II Studie mit modifizierten autologen MSC_apceth_101

A.3.2

Name or abbreviated title of the trial where available

TREAT-ME 1

A.4.1

Sponsor's protocol code number

MSC_apceth_101/1

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	apceth 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	apceth GmbH & Co. KG
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	apceth GmbH & Co. KG
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Haidgraben 5
B.5.3.2	Town/ city	Ottobrunn
B.5.3.3	Post code	85521
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4989700 9608178
B.5.5	Fax number	+4989700 9608160
B.5.6	E-mail	s.oellerer@apceth.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	MSC_apceth_101
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Cymeven i.v.
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Pharma AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Cymeven i.v.
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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)	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

Patients suffering from advanced, recurrent or metastatic gastrointestinal adenocarcinoma.

E.1.1.1

Medical condition in easily understood language

Patients suffering from advanced, recurrent or metastatic gastrointestinal adenocarcinoma.

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	HLGT
E.1.2	Classification code	10017991
E.1.2	Term	Gastrointestinal neoplasms malignant and unspecified
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

To evaluate the safety and tolerability of MSC_apceth_101

Die Evaluierung der Sicherheit und Verträglichkeit von MSC_apceth_101

E.2.2

Secondary objectives of the trial

• Efficacy based on RECIST criteria and on tumor/serum markers
• Quality of life

• Wirksamkeit basierend auf den ‘RECIST‘ Kriterien und auf Basis von Tumor- oder Serum-Markern
• Lebensqualität

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with advanced or recurrent or metastatic gastrointestinal adenocarcinoma.
Target indications:
cancer of the esophagus (cTNM: T3NxMx or T4NxMx);
pancreatic (cTNM: T3NxMx); or
gastric cancer (cTNM: T3NxMx or T4NxMx); or
intrahepatic cholangiocellular carcinoma (cTNM: T3NxMx or T4NxMx); or
metastases due to colorectal cancer (cTNM: TxNxM1).
The TNM classification should not be older than 4 months.

2. Premature or scheduled termination of standard therapy (including possible preoperative therapy) due to intolerability / progress / inefficacy or no acceptance by the patient if re-lapses/metastases are measurable by means of imaging techniques. No relapse and no metastases should exceed 5 cm in its maximal diameter.

3. In case of metastases due to colorectal cancer:
• Metastases are unresectable
• The total volume of the liver metastases does not exceed 30 % of the total liver volume
• In addition to liver metastases lung metastases (as assessed by a radiologists with a minimum diameter of at least 0.5 cm) are allowed, however, not more than 10 with the largest one not exceeding 2 cm in diameter
• Lymph node metastases are permitted
• Brain metastases: As long as only one organ is affected by extra-cranial metastases due to colorectal cancer no radio-logical investigation for brain metastases is needed if there are no signs or symptoms suspicious for brain metastases. In case of liver and lung metastases the patient has to be excluded unless a cranial image verifies absence of brain metastases

4. Patients who have donated bone marrow for the production of MSC_apceth_101 based on a separate approved protocol. MSC_apceth_101 must have been released for the (autologous) use in the same patient.

5. Progressive disease as clinically assessed by the investigator.

In addtion:
A.1 Adequate organ function:
a. Hb > 9.0 g/dl
b. WBC > 3,000 cells/µl
c. Neutrophils >500 /μl
c. Platelets > 100,000 cells/µl
d. ALT/AST ≤ 3 ULN
(or ≤ 5 ULN in case of intrahepatic cholangiocellular carcinoma)
e. total bilirubin ≤ 1.5 ULN
(or ≤ 2 ULN in case of intrahepatic cholangiocellular carci-noma)
f. Creatinine ≤ 2.0 mg/dl
g.Creatinine clearance ≥ 50 ml/min

A.2 Anticipated minimal life expectancy of at least 6 months

A.3 Men and women of reproductive potential must agree to follow accepted contraception methods during treatment and for 3 months after completion of treatment. Medically acceptable methods of birth control are methods with a low failure rate of less than 1% per year; e.g. hormonal contraceptives for at least the 7 days before trial enrolment or an intrauterine device, or double barrier method (male or female condom or diaphragm, in com-bination with a spermicidal gel). All women, including those with tubal ligation, are considered to be of childbearing potential unless they have been postmenopausal for at least 2 years. Hysterectomized women are considered surgically sterile and are not required to use any contraception.
Males should not participate in a sperm donation program.

A.4 Ability of patient to understand character and individual consequences of clinical trial

A.5 Age ≥ 18 years

A.6 Written informed consent must be available before any study specific procedure is performed

E.4

Principal exclusion criteria

1. Patients with severe heart diseases (NYHA stage three and four; unstable angina pectoris, or myocardial infarction during the last 8 weeks before Visit 1 (Baseline))

2. Clinical significant ischemic disease during the last 4 weeks before Visit 1 (Baseline)

3. Severe lung disease (COPD Grade III, Asthma bronchiale Grade IV, lung fibrosis)

4. General condition worse than ECOG 2

5. Symptomatic peritoneal carcinomatosis (e.g. by the presence of ascites)

6. Symptomatic pleural or pericardial effusion

7. Serious uncontrolled acute infections less than 3 weeks before Visit 1 (Baseline)

8. Patients with HCV infection as defined by anti-HCV pos and HCV RNA pos and / or HBV in-fection as defined by anti-Hbc pos and/ or HBV DNA pos

9. Patients with HIV infection as minimally demonstrated by HIV RNA

10. Immunodeficiencies or systemic autoimmune diseases (e.g. M. Crohn, Colitis ulcerosa) or known malformations of the gastrointestinal tract

11. Active infection with HSV (by IgM pos)

12. Second carcinoma in addition to the underlying carcinoma unless the second carcinoma was curatively and successfully resected more than 5 years ago before Visit 1 (Baseline) (exception: basal cell carcinoma, precancerous conditions)

13. Use of any immunomodulators

14. Need for chemotherapy or radiotherapy or cytokine treatment (e.g. interferons, G-CSF or GM-CSF) in the time interval 2 weeks before infusion of MSC_apceth_101 or anticipation of chemo- or radiotherapy during treatment with MSC_apceth_101 and GCV until 2 days after the last administration of GCV

15. Known dependency on alcohol or other drugs

16. Patients requiring corticoids in doses above the Cushing threshold

17. Known liver fibrosis or liver cirrhosis

18. Any concomitant severe disease which could compromise the objectives of this study in the judgment of the investigator

19. Female patient who is pregnant or breast feeding

20. Participation in another clinical trial or observation period, respectively, during the last 4 weeks prior to the first MSC_apceth_101 dose

21. Any surgery in the last four weeks before the administration of MSC_apceth_101

22. History of hypersensitivity to the investigational product or to Ganciclovir, Valganciclovir, Aciclovir or Valaciclovir

23. Any contraindication to Ganciclovir (see package insert) or the need for the following drugs interacting with Ganciclovir: Probenecid; combination of Imipenem-Cilastatin; Dapson, Pen-tamidin; Flucystosin; Vincristin, Vinblastin, Adriamycin, Amphotericin B; combination of Tri-methoprim and Sulfonamides, Nucleosideanaloga or Hydroxy-urea. This is confined to the time period 14 days prior to Ganciclovir and up to 7 days after termination of Ganciclovir treatment.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints, safety and tolerability of MSC_apceth_101 will be assessed by:
• Adverse event listings and tables based on MedDRA terms, severity grade, relationship to both study medications and CTC-AE grades
• Listings for laboratory values. Additionally, descriptive statistics will be provided for laboratory parameters.
• For all other safety data, listings and descriptive statistics (for continuous variables) or frequency tables (for categorical variables) will be provided.

E.5.1.1

Timepoint(s) of evaluation of this end point

2 months after first treatment with MSC_apceth_101.

E.5.2

Secondary end point(s)

Secondary endpoints will be
imaging results obtained by CT or MRT (classified by RECIST criteria),
laboratory data for tumor and serum markers,
the overall survival of patients and time to tumor progression.

E.5.2.1

Timepoint(s) of evaluation of this end point

2 months after first treatment with MSC_apceth_101.

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

Yes

E.6.13.1

Other scope of the trial description

proof of concept

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

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

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

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

The study is completed at the time the last patient enrolled has completed all reasonable investigations of day 56 (2 months). It is the final visit 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 - only normal or standard therapy, respectively.

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

2013-05-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-27

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

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