Clinical Trials Register

Summary
EudraCT Number:	2013-001664-34
Sponsor's Protocol Code Number:	12028-FC-SS
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-07-26
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

UK - MHRA

A.2

EudraCT number

2013-001664-34

A.3

Full title of the trial

Vit-D in CRC - A Randomised Double Blind Placebo-Controlled Clinical Trial Of a Single Oral Cholecalciferol Treatment Against Surrogate End Point Biomarkers (SEBs) In Colon Cancer (CRC) Patients

A.3.1

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

Effects of Vitamin D on factors that predict bowel tumour growth

A.3.2

Name or abbreviated title of the trial where available

Vitamin D growth control biomarkers in colorectal cancer (CRC)

A.4.1

Sponsor's protocol code number

12028-FC-SS

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	Belfast HSC Trust
B.1.3.4	Country	United Kingdom
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	Cancer Research UK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	N. Ireland Cancer Trials Center
B.5.2	Functional name of contact point	Prof Campbell
B.5.3	Address:
B.5.3.1	Street Address	Belfast City Hospital, Lisburn Road
B.5.3.2	Town/ city	Belfast
B.5.3.3	Post code	BT9 7AB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02890638468
B.5.5	Fax number	02890263897
B.5.6	E-mail	f.c.campbell@qub.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	Queens University Belfast
B.1.3.4	Country	United Kingdom
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	Cancer Research Uk
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	as previous B5
B.5.2	Functional name of contact point

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	Vigantol Oil
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck
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	Vigantol Oil (Cholecalciferol)
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Oral liquid
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	1 alpha 25-dihidroxy vitamin D3 (INN - Calcitriol)
D.3.9.1	CAS number	CAS 67-97-0
D.3.9.2	Current sponsor code	N/a
D.3.9.3	Other descriptive name	Calcitriol
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20,000 units to ml
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.4	EV Substance Code	AS2
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral liquid
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Colon cancer

E.1.1.1

Medical condition in easily understood language

Bowel tumours

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	16.0
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

Principal objective
To assess effects of Vit-D levels that are known to suppress cancer on the concentration of a surrogate endpoint biomarker (SEB) called CYP27B1 in the bowel. CYP27B1 converts blood Vit-D into a more active form.

E.2.2

Secondary objectives of the trial

Secondary objectives include
(i) assessment of Vit-D treatment effects on other SEBs in normal bowel and (ii) bowel tumours.
(iii) Investigation of relationships between SEBs and tumour aggressiveness, assessed in 3 grades under the microscope.
(iv) Mutation in the K-ras gene can cause Vit-D resistance and will be investigated in bowel tumours.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Over 200 new patients with bowel tumours present to the Belfast Trust each year. Approximately 240 patients will be invited to participate throughout the
study interval to enable study completion with 120 patients.

Inclusion criteria include patients aged 30-90 of either sex with a sporadic primary operable bowel tumour, presenting to the Belfast Hospitals Trust who have adequate kidney, liver and bone marrow function, Eastern cooperative oncology group (ECOG) performance status <2.0 (Karnofsky ≥70%), free of distant metastases and who are agreeable to avoidance of any concurrent Vit-D supplementation outwith the study. Completion of imaging including computed tomography (CT) or barium enema and ECG are inclusion criteria. Ability to understand and the willingness to sign a written informed consent document are essential. Because participants aged less than 30 years with CRC have a higher incidence of colitis-associated or genetically predisposed cancer that may be undetected at diagnosis, patients aged <30 years will be excluded. Participants must have normal organ and marrow function as defined below:
Leukocytes- ≥3,000/ml, Absolute neutrophil count - ≥1,500/ml;Platelets- ≥100,000/ml; Total bilirubin-within normal limits; AST (SGOT)/ALT (SGPT)- ≤1.5 X Upper limit of normal; Creatinine- within normal limits;Serum calcium -≤2.6mmlol/l. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

E.4

Principal exclusion criteria

Colitis-associated or hereditary colorectal cancer, hypercalcaemia, hyperparathyroidism, diabetes mellitus, steroid, anticoagulant or concurrent Vitamin D therapy, skeletal or liver metastases, ECG indication of recent myocardial instability, ECOG performance status >2.0, impairment of kidney or liver function evidenced by persistent elevation of serum urea and/or bilirubin, inability to obtain paired pre- and post-treatment tumour biopsies for analysis. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are all exclusion criteria. Pregnant women are excluded from this study because effects of high dose Vit-D on the developing foetus are unknown. Failure of tissue sampling or other relevant methodology comprise exclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

To test effects of cancer-suppressive serum Vit-D levels on CYP27B1 expression in the bowel.

E.5.1.1

Timepoint(s) of evaluation of this end point

Expression of CYP27B1 in human colon. This will be assessed at three weeks after a single high dose of oral Vitamin D.

E.5.2

Secondary end point(s)

Secondary objectives will assess
(i) Expression, interrelationships and treatment effects on SEBs in normal mucosa
(ii) SEB responses in CRC vs normal mucosa
(iii) SEB associations with histopathological CRC prognostic factors
(iv) Associations between CRC K-Ras genotype and SEB responses

E.5.2.1

Timepoint(s) of evaluation of this end point

The above endpoints will be assessed at 3 weeks after a single high dose of Vitamin D.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3

Other

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

LVLS

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