Clinical Trials Register

Summary
EudraCT Number:	2010-024354-11
Sponsor's Protocol Code Number:	ABCSGR05
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-01-25
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

Austria - BASG

A.2

EudraCT number

2010-024354-11

A.3

Full title of the trial

Preoperative induction chemotherapy in combination with Bevacizumab followed by combined chemoradiotherapy in locally advanced rectal cancer with high risk of recurrence- phase II pilot study with preoperative administration of Capecitabine (Xeloda), Oxaliplatin and Bevacizumab (Avastin) followed by Capecitabine (Xeloda) plus Radiotherapy (RTx)

Präoperative Induktionschemotherapie in Kombination mit Bevacizumab gefolgt von kombinierter Radiochemotherapie des lokal fortgeschritten Rektumkarzinoms mit hohem Rezidivrisiko – eine Phase II Pilotstudie mit präoperativer Gabe von Capecitabine (Xeloda), Oxaliplatin und Bevacizumab (Avastin), gefolgt von Capecitabine (Xeloda) plus Radiotherapie (RTx)

A.3.1

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

Phase II pilot study of a preoperative induction chemotherapy in combination with Bevacizumab followed by combined radiochemotherapy for patients with locally advanced rectal carcinoma

A.4.1

Sponsor's protocol code number

ABCSGR05

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	ABCSG (Austrian Breast & Colorectal Cancer Study Group)
B.1.3.4	Country	Austria
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	Roche Austria GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ABCSG (Austrian Breast & Colorectal Cancer Study Group)
B.5.2	Functional name of contact point	Studienzentrale (Trial Office)
B.5.3	Address:
B.5.3.1	Street Address	Nussdorfer Platz 8
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1190
B.5.3.4	Country	Austria
B.5.4	Telephone number	+431408 92 30
B.5.5	Fax number	+431409 09 90
B.5.6	E-mail	info@abcg.at

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 Registration Ltd.
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	Avastin
D.3.2	Product code	RO487-6646
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	BEVACIZUMAB
D.3.9.1	CAS number	216974-75-3
D.3.9.2	Current sponsor code	RO487-6646
D.3.9.3	Other descriptive name	rhuMAb, VEGF, anti-VEGF
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	25
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)	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	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.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 Registration Ltd.
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	Xeloda
D.3.2	Product code	RO009-1978
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAPECITABINE
D.3.9.1	CAS number	154361-50-9
D.3.9.2	Current sponsor code	RO09-1978
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	150 to 500
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.2.5	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.3.4	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	61825943
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	130
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

locally advanced rectal cancer with high risk of recurrence

E.1.1.1

Medical condition in easily understood language

locally advanced rectal 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

feasibility and tolerance of a preoperative induction chemotherapy in combination with Bevacizumab followed by combined radiochemotherapy with Capecitabine for patients with locally advanced rectal carcinoma

E.2.2

Secondary objectives of the trial

Assessment of the respond rate (R0 rate, downstaging of the T- and N-stage), evaluation of the postoperative morbidity according to Accordeon at the day of release from the inpatient stay

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age 18-80 years
• Histologic confirmation of rectal andenocarcinoma stage cT3 (≤ 5mm to the mesorectal fascia)/cT4( primary curative intention)NxM0
• No former chemotherapy, no former radiotherapy of the pelvic, no former tumour resection of a rectal carcinoma
• General condition WHO grade 0-2
• Adequate bone marrow reserve ( leucocytes ≥3 000/µl, thrombocytes ≥100 000/µl)
• Adequate renal function (creatinine ≤ 1,5 mg/dl, creatinine clearence > 50ml/min (Cockroft and Gault formula))
• Adequate liver function (bilirubin ≤1,5x ULN, GOT and GPT ≤3,5x ULN)
• Exclusion of pregnancy for women with childbearing potential (negative pregnancy test urine or serum)
• Female patients with childbearing potential and male patients that are not surgically sterile must be practicing a medically acceptable contraceptive regimen while on study treatment until 3 months after the end of the study (e.g. oral contraceptives, condom, intrauterine device)
• Life expectancy of at least 3 months
• INR and aPTT ≤ 1,5 x LLN
• Provision of signed informed consents before registration

E.4

Principal exclusion criteria

• Rectal carcinoma stage cT3 (> 5mm from the mesorectal fascia) all stages <cT3, M1
• Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
• General contraindication or known hypersensitivity against Bevacizumab, Capecitabine and Oxaliplatin
• Not malignant diseases for which treatment with radiotherapy, resection of the rectum and treatment with chemotherapy (Bevacizumab, Capecitabine) is contraindicated:
uncontrolled hypertension (systolic > 150 mmHG and/or diastolic > 100 mmHG) or clinically significant (e.g. active) cardiovascular diseases: CVA (cardiovascular accident)/ apoplectic insult (≤ 6 months prior to registration), myocardial infarction (≤ 6 months prior to registration), unstable angina pectoris, CHF(congestive heart failure) with NYHA (New York heart Association) Grade II or higher, cardiac arrhythmia requiring therapy, hepatic diseases, significant neurologic or psychiatric disorders
• Florids, serious infection at registration
• Peripheral neuropathy (NCI CTCAE v 4.0 ≥ grade 1)
• Juridically limited contractual capability, indication of neurological or psychiatric disease which constrains upon investigators opinion the patients capability to adhere to the study routines
• Major surgical procedure within 28 days prior start of the study, open wounds
• Significant traumatic injury, bone fracture, unhealed wounds
• Patients with spinal cord compression or metastases in the central nervous system
• Indication of bleeding diathesis or coagulopathy
• Intake of anticoagulant or thrombolytic agents and/or Aspirin > 325 mg/d within 10 days prior to registration
• Current or recent (within 10 days prior to treatment start) therapy with full dosed anticoagulants. Preventive therapy is allowed.
• Previous thromboembolic or haemorrhagic events within 6 months prior to registration
• Previous abdominal fistulas, gastro-intestinal perforation or intra-abdominal abscesses within 6 months prior to registration
• Treatment with another investigational drug within 28 days prior to registration
• Patients with malabsorbtion syndrome or difficulties in swallowing
• Indication of poor compliance of the patient
• Pregnant or breast-feeding women
• Proteinuria: Dipstick <2+. If the Dipstick is ≥2+ protein has to be estimated in the 24 hours urine. The value should not be higher then 1g/24 hours.

E.5 End points

E.5.1

Primary end point(s)

termination of therapy, occurrence of toxicity

E.5.1.1

Timepoint(s) of evaluation of this end point

- termination of therapy: before surgery (after conclusion of therapy phase)
- occurence of toxicity: until the timepoint of discharge of patient

E.5.2

Secondary end point(s)

downstaging of the T- and N-stage, occurrence of pathological complete remission, post-surgery morbidity according to Accordion

E.5.2.1

Timepoint(s) of evaluation of this end point

- downstaging of the T- and N-stage, occurrence of pathological complete remission: at the timepoint of surgery
- morbitdity: at the timepoint of discharge of patient

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

E.6.5

Efficacy

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

feasibility and tolerance of a preoperative induction chemotherapy

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

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

End of study = day of release from the inpatient stay after surgery

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)

standard after-care outside the protocol

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

2011-03-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-08-26

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