Clinical Trials Register

Summary
EudraCT Number:	2014-002665-30
Sponsor's Protocol Code Number:	RENAISSANCE
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-10-09
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 - BfArM

A.2

EudraCT number

2014-002665-30

A.3

Full title of the trial

Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction – a phase III trial of AIO/CAO-V/CAOGI

Effekt von Chemotherapie alleine vs. Chemotherapie gefolgt von operativer Resektion auf Überleben und Lebensqualität bei Patienten mit limitiert-metastasiertem Adenokarzinom des Magens oder des ösophagogastralen Übergangs – eine Phase III Studie der AIO/CAO-V/CAOGI

A.3.1

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

Comparison of the effect of a chemotherapy alone to a chemotherapy combined with surgical resection on the survival and the quality of life of patients with limited metastatic cancer of the stomach or esophagus

Vergleich der Auswirkungen einer Chemotherapie alleine gegenüber einer Chemotherapie zusammen mit einer Operation auf das Überleben und die Lebensqualität von Patienten mit eingeschränkt metastasiertem Magen- oder Speiseröhrenkrebs

A.3.2

Name or abbreviated title of the trial where available

Renaissance / FLOT5

A.4.1

Sponsor's protocol code number

RENAISSANCE

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	Krankenhaus Nordwest gGmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Deutsche Forschungsgemeinschaft (DFG)
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	Institut für Klinisch-Onkologische Forschung, Krankenhaus Nordwest gGmbH
B.5.2	Functional name of contact point	IKF
B.5.3	Address:
B.5.3.1	Street Address	Steinbacher Hohl 2-26
B.5.3.2	Town/ city	Frankfurt/M.
B.5.3.3	Post code	60488
B.5.3.4	Country	Germany
B.5.4	Telephone number	00496976014420

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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Docetaxel
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	docetaxel
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB12492MIG
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.2.1.2	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	Oxaliplatin
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OXALIPLATIN
D.3.9.1	CAS number	61825-94-3
D.3.9.4	EV Substance Code	SUB09490MIG
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: 3
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.2.1.2	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	5-fluorouracil
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	5-fluorouracil
D.3.9.3	Other descriptive name	FLUOROURACIL
D.3.9.4	EV Substance Code	SUB07721MIG
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: 4
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.2.1.2	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	leucovorin
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CALCIUM FOLINATE
D.3.9.3	Other descriptive name	CALCIUM FOLINATE
D.3.9.4	EV Substance Code	SUB06052MIG
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

limited-metastatic adenocarcinoma of the stomach or esophagogastric junction

E.1.1.1

Medical condition in easily understood language

limited-metastatic gastric cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Overall survival (OS)
(The duration of OS will be determined by measuring the time interval from randomization to the date of death or last observation (censored))

E.2.2

Secondary objectives of the trial

•Quality of life (QoL) adjusted OS
•QoL-response
•QoL mean scores
•OS in patients with lymph node metastases only
•Progression free survival (PFS): time interval from randomization until disease progression or disease recurrence after surgery or death of any cause
•Surgical morbidity and mortality
•Toxicity

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Histologically confirmed limited metastatic gastric or GEJ adenocarcinoma.*
2.Medical and technical operability of the primary.
3.Metastatic lesions are resectable or can be controlled by local ablative procedure (central evaluation).
4.No prior chemotherapy and no prior tumor resection.
5.Female and male patients >18 years. Patients in reproductive age must be willing to use adequate contraception during the study and 3 months after the end of the study (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: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
6.ECOG 0 or 1
7.Adequate hematological, hepatic and renal function parameters:
-Leukocytes ≥ 3000/µl
-Platelets ≥ 100,000/µl
-Serum creatinine ≤ 1.5 x upper limit of normal, or GFR > 40 ml/min
-Bilirubin ≤ 1.5 x upper limit of normal
-AST and ALT ≤ 3.5 x upper limit of normal
-Alkaline phosphatase ≤ 6 x upper limit of normal
8.Written informed consent of the patient.

(*) Definition of the limited metastatic status according Flot3-study with modification is:
1.Retroperitoneal lymph node metastases (RPLM) (e.g., para-aortal, intra-aorto-caval, parapancreatic or mesenterial lymph nodes) only
or/and
2.at maximum one organ involved with or without RPLM according to the following schema:
I.Localized potentially operable peritoneal carcinomatosis: stage P1 according to classification of the „Japanese Research Society for Gastric Cancer“ (Clinically visible carcinomatosis of the peritoneum or of the pleura and >P1 peritoneal carcinomatosis are not allowed!) or
II.Liver: maximum of 5 metastatic lesions that are potentially resectable or
III.Lung: unilateral involvement, potentially resectable or
IV.Uni- or bilateral Krukenberg tumors (ovarian met.) in the absence of macroscopic peritoneal carcinomatosis or
V.Uni- or bilateral adrenal gland metastases or
VI.Extra-abdominal lymph node metastases such as supraclavicular lymph node involvement or
VII.Localized bone involvement (defined as being within one radiation field) or
VIII.Other metastatic disease location that is considered limited by the investigator and is confirmed by the review committee

E.4

Principal exclusion criteria

1.Medical inoperability
2.Inability to understand the aims of the study and/or protocol procedures
3.Metastatic disease not fulfilling the criteria of limited disease mentioned in the inclusion criteria or non-metastatic stage (cM0)
4.Cirrhosis of the liver, pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
5.Primary not resectable
6. Hypersensitivity to 5-fluorouracil, leucovorin, oxaliplatin, or docetaxel
7. Contraindication versus 5-fluorouracil, leucovorin, oxaliplatin, or docetaxel (see specific product information)
8.Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV
9.Clinically significant valvular defect
10.Past or current history of other malignancies unless curatively treated and without evidence of disease for more than 3 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix
11.Known brain metastases
12.Other severe internal disease or acute infection
13.Peripheral polyneuropathy > NCI grade II
14.Serious hepatic impairment (AST/ALT>3.5xULN, AP>6xULN, bilirubin>1.5xULN)
15.Chronic inflammatory bowel disease
16.Any other concurrent antineoplastic treatment including irradiation
17.Participation in another clinical study
18.Pregnancy or lactation

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

continuously

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

•Quality of life (QoL) adjusted OS - continuously
•QoL-response - continuously
•QoL mean scores - end of study
•OS in patients with lymph node metastases only - continuously
•Progression free survival (PFS) - continuously
•Surgical morbidity and mortality - after surgery

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Combination of chemotherapy with surgical intervention will be compared to chemotherapy alone

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

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

Database closure is defined as the end of the trial: Sites need to collect survival data of patients and are involved in the data cleaning process actively (e.g. additional source data may be requested and additonal monitoring visits may be neccessary). Therefore, database closure is considered the end of the trial.

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

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:

271

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

271

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

271

F.4.2

For a multinational trial

F.4.2.1

In the EEA

271

F.4.2.2

In the whole clinical trial

271

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)

The investigators of the study are experienced medical or surgical oncologists who treat patients in routine clinical practice. Therefore, the investigators are responsible for the further treatment of the patient after the end of the study for disease progression. The investigators shall support and advice the patient and – if required – help to
organize appointments with other specialized physicians.
See protocol sections 15.2.3, 17.9, and 17.10 for further details.

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

2015-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-11

P. End of Trial
P.	End of Trial Status	Ongoing

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