Clinical Trials Register

Summary
EudraCT Number:	2011-003137-33
Sponsor's Protocol Code Number:
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-09-08
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

Finland - Fimea

A.2

EudraCT number

2011-003137-33

A.3

Full title of the trial

Open-label, single-arm, phase II study of bevacizumab (AVASTIN) in combination with alternating Xeliri and Xelox as first-line treatment of patients with metastatic colorectal cancer

II vaiheen avoin tutkimus: bevasitsumabin, kabesitabiinin ja vuorotellen annettavan irinotekaani ja oksaliplatiini olunsalpaajahoidon yhdistelmä potilailla, jotka sairastavat etäpesäkkeistä suolistosyöpää

A.3.1

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

Bevasitsumabin, kabesitabiinin ja vuorotellen annettavan irinotekaani ja oksaliplatiini solunsalpaajahoidon yhdistelmä potilailla, jotka sairastavat etäpesäkkeistä suolistosyöpää

A.3.2

Name or abbreviated title of the trial where available

AXOAXI

A.4.1

Sponsor's protocol code number

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	Pia österlund and Helena Isoniemi
B.1.3.4	Country	Finland
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pia Österlund
B.5.2	Functional name of contact point	Helsinki University Hospital
B.5.3	Address:
B.5.3.1	Street Address	Haartmaninkatu 4, PL 180
B.5.3.2	Town/ city	Helsinki
B.5.3.3	Post code	00029 HUS
B.5.3.4	Country	Finland
B.5.4	Telephone number	35894711
B.5.5	Fax number	358947174204
B.5.6	E-mail	pia.osterlund@hus.fi

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.2.1.1.1	Trade name	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche oy
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	Avastin
D.3.4	Pharmaceutical form	Concentrate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 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	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.3.11.13.1	Other medicinal product type	humanized monoclonal antibody
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	Xeloda
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Oy
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	Xeloda
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral 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

metastatic colorectal cancer

E.1.1.1

Medical condition in easily understood language

levinnyt suolistosyöpä

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

- PFS
- To assess overall resectability in patients with metastatic colorectal cancer, postoperative morbidity and outcomes after resection

E.2.2

Secondary objectives of the trial

- To assess response rates according to RECIST criteria, failure free survival (TTF) and overall survival (OS)
- Quality of life according to 15D questionnaire
- To radiologically assess tumor density and morphology, and assess alternative radiologic response evaluation in comparison with RECIST response criteria
- Biomarker evaluation to measure plasma biomarkers, tumor blocks and DNA polymorphisms that may predict drug effects, safety, and clinical behavior of the tumor

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria
1. Patients with histologically confirmed diagnosis of CRC, chemotherapy naïve for metastatic disease (prior adjuvant chemotherapy more than 6 months previously for CRC allowed), who are scheduled to start first line chemotherapy for metastatic disease
2. Age  18
3. Measurable or evaluable metastatic disease
4. Performance status ECOG performance status 0-2
5. Life expectancy greater than 3 months
6. Thrombocytes  100’000/l, neutrophils  1’500/µl, Aspartate amino transferase/Alanine amino transferase  2.5  Upper limit of normal (ULN) (≤ 5  ULN if liver metastases present), Alkaline phosphatase  2.5  ULN (≤ 5  ULN if liver metastases present), Serum bilirubin  1.5  ULN, Serum Creatinine  1.5  ULN, Urine dipstick of proteinuria <2+ (or U-Prot <100mg/dl). Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, must undergo a 24-hour urine collection and must have  1 g of protein/24 hr
7. Women of childbearing potential must have a negative serum pregnancy test done prior to the administration of bevacizumab. Patient and their partner should have adequate contraception up to at least 6 months after last treatment completion or the last drug dose, whatever happens first
8. Signed written informed consent according to ICH/GCP and the local regulations (approved by the Independent Ethics Committee [IEC]) will be obtained prior to any study specific screening procedures
9. Patient must be able to comply with the protocol

E.4

Principal exclusion criteria

Exclusion criteria
1. Prior treatment with first-line chemotherapy for metastatic CRC
2. Adjuvant treatment within 6 months
3. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 (Patients must have recovered from any major surgery)
4. Near future planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed)
5. Clinical or radiological evidence of CNS metastases
6. Past or current history within the last 2 years of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin or in-situ carcinoma of the cervix
7. Serious non-healing wound or ulcer
8. Evidence of bleeding diathesis or coagulopathy
9. Uncontrolled hypertension
10. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
11. Treatment with any investigational drug within 30 days prior to enrolment
12. Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the treatment or patient at high risk from treatment complications
13. Chronic daily intake of aspirin (> 325 mg/day) or clopidogren (> 75 mg/day)
14. Pregnancy (positive serum pregnancy test) and lactation
15. Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial

E.5 End points

E.5.1

Primary end point(s)

PFS, resectability rate

E.5.2

Secondary end point(s)

- response rates, failure free survival (TTF) and overall survival (OS)
- Quality of life stionnaire
- tumor density and morphology and alternative radiologic response evaluation
- Biomarker evaluation

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)

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

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

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
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.4.2.2	In the whole clinical trial	100

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

2011-10-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-14

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

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