Clinical Trials Register

Summary
EudraCT Number:	2015-004240-19
Sponsor's Protocol Code Number:	ALASCCA
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-02-23
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

Denmark - DHMA

A.2

EudraCT number

2015-004240-19

A.3

Full title of the trial

A randomized double-blind placebo-controlled study with ASA treatment in
colorectal cancer patients with mutations in the PI3K signaling pathway

A.3.1

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

ALASCCA-A randomized double-blind placebo-controlled study with ASA
treatment in colorectal cancer patients with mutations in the PI3K
signaling pathway.

A.4.1

Sponsor's protocol code number

ALASCCA

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	Karolinska University Hospital, Department of Molecular medicine and Surgery Karolinska Institutet, Gastrocentrum
B.1.3.4	Country	Sweden
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	The Swedish Research Council
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Karolinska Institute
B.5.2	Functional name of contact point	Coordinating Investigator
B.5.3	Address:
B.5.3.1	Street Address	Department of Molecular medicine and Surgery Karolinska Institutet, Gastrocentrum
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	17176
B.5.3.4	Country	Sweden
B.5.6	E-mail	Anna.Martling@ki.se

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	Trombyl
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer AB
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	Trombyl
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ACETYLSALICYLIC ACID
D.3.9.1	CAS number	50-78-2
D.3.9.4	EV Substance Code	SUB12730MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	160
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	Tablet
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 or rectal cancer tumor stage II-III, tumor with somatic alterations
in PIK3CA, PIK3R1 or PTEN.

E.1.1.1

Medical condition in easily understood language

Colon or rectal cancer.

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10010029
E.1.2	Term	Colorectal cancer NOS
E.1.2	System Organ Class	100000004864

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 determine whether adjuvant treatment with 160 mg ASA once daily
for 3 years can improve Time To Recurrence (TTR) in patients with
colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20)
compared with placebo.

E.2.2

Secondary objectives of the trial

To determine whether adjuvant treatment with 160 mg ASA once daily
for 3 years can improve Disease-Free Survival (DFS) in patients with
colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20)
compared with placebo.
To determine whether adjuvant treatment with 160 mg ASA once daily
for 3 years can improve DFS in patients with colorectal cancer with
somatic alterations in the PIK3CA (other than exon 9 and 20), PIK3R1 or
PTEN genes compared with placebo.
To determine whether adjuvant treatment with 160 mg ASA once daily
for 3 years can improve TTR in patients with colorectal cancer with
somatic alterations in the PIK3CA (other than exon 9 and 20), PIK3R1 or
PTEN genes compared with placebo
To compare overall survival (OS) at 5 years from randomization in
patients receiving low-dose ASA versus placebo.
To assess overall safety and tolerability.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Tumor with somatic alterations in PIK3CA, PIK3R1 or PTEN
- Colon or rectal cancer tumor stage II-III
- Patient between18-80 years (including)
- Radical surgery according to surgeon and pathologist
- Karnofsky performance status ≥70%
- Platelets ≥ 100 x 109 / L
- Clean Colonoscopy or Computed Tomography (CT) colon within 3
months preoperatively or postoperatively but before randomization
- Patient able to swallow tablets

E.4

Principal exclusion criteria

Hereditary colorectal cancer linked to familial colonic polyposis or
Lynch syndrome
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
- Distant metastases
- Other cancers (excluding colorectal cancer or other skin cancer than
melanoma) within 3 years from screening
- Known bleeding diathesis (such as hemophilia)
- Concomitant antiplatelet therapy (eg clopidrogrel or ticlopidine) or
anticoagulant therapy (warfarin or low molecular weight heparin).
Postoperative
treatment with low molecular weight heparin must be
withdrawn before administration of study treatment
- Active gastritis or peptic ulcer, or significant surgical post-op bleeding,
within the previous three months assessed at screening and
randomization
- Ongoing regular use of corticosteroids, Nonsteroidal Anti-Inflammatory
Drug (NSAID)
- Uncontrolled hypertension according to Investigator's judgment
- Clinically significant liver impairment according to Investigators
judgment
- Existing renal failure according to Investigator's judgment. Renal
failure with decreased creatinine clearance <60 should lead to
consultation with a nephrologist.
- Significant medical illness that would interfere with study participation
- Pregnancy or breastfeeding females
- Known allergy to NSAIDs or ASA
- Current participation in another clinical trial that will be in conflict with
the present study
- Patients who are unlikely to comply with the protocol (e.g.
uncooperative attitude, inability to return for subsequent visits) and/or
otherwise considered by the Investigator to be unlikely to complete the
study
Patients with regular administration of ASA, defined as >3 doses/week,
will be included in the observation group. Other additional regular use of
ASA must be withdrawn before randomization.

E.5 End points

E.5.1

Primary end point(s)

Time To Recurrence (TTR) at 3 years in patients with tumors harboring
PIK3CA mutations in exon 9 and 20.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 years.
Interim analyses on the safety endpoints after one year.

E.5.2

Secondary end point(s)

Disease-Free Survival (DFS) at 3 years, in patients with tumors
harboring PIK3CA mutations in exon 9 and 20.
Disease-Free Survival (DFS) at 3 years, in patients with tumors
harboring PIK3CA mutations other than in exon 9 and 20 and in PIK3R1
and PTEN.
Time To Recurrence (TTR) at 3 years, in patients with tumors harboring
PIK3CA mutations other than in exon 9 and 20 and in PIK3R1 and PTEN.
OS at 5 years in patients with tumors harboring PIK3CA mutations in
exon 9 and 20, other than in exon 9 and 20, and in PIK3R1 and PTEN.

E.5.2.1

Timepoint(s) of evaluation of this end point

3 years.
Interim analyses on the safety endpoints after one year.

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Stratification based on clinical stage, cancer localisation (rectal/colon), type of mutation.

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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:

326

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

490

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

816

F.4.2.2

In the whole clinical trial

816

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.

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

2017-05-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-07

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

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