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

Status Authorised, recruitment pending · 4 EU/EEA countries · 33 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Authorised, recruitment pending

Participants planned 700

Countries 4

Sites 33

Colon and rectal cancer tumor stage II-III, tumor with somatic alterationsin PIK3CA, PIK3R1 or PTEN

To determine whether adjuvant treatment with 160 mg Acetylsalicylic Acid (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.

Key facts

Sponsor: Karolinska Institutet
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Decision date (initial): 2024-10-03
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes
Funding sources: The Swedish research Council

External identifiers

EU CT number: 2024-513778-23-00
EudraCT number: 2015-004240-19
ClinicalTrials.gov: NCT02647099

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Secondary objectives 5

• 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 compared with placebo.
• To assess overall safety and tolerability.

Conditions and MedDRA coding

Colon and rectal cancer tumor stage II-III, tumor with somatic alterationsin PIK3CA, PIK3R1 or PTEN

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

- Tumor with somatic alterations in PIK3CA, PIK3R1 or PTEN
- Colon cancer tumor stage II-III or rectal cancer tumor stage I-III
- Patient between18-80 years (including)
- Radical surgery according to surgeon and pathologist
- Karnofsky performance status ≥60%
- 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
- Patient able to understand and sign written informed consent

Exclusion criteria 15

- 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). Post-operative 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

• TTR at 3 years, in patients with tumors harboring PIK3CA mutations in exon 9 and 20

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Trombyl 160 mg tabletter

PRD412040 · Product

Active substance: Acetylsalicylic Acid
Pharmaceutical form: TABLET
Route of administration: ORAL
Max daily dose: 160 mg milligram(s)
Max total dose: 160 mg milligram(s)
Max treatment duration: 36 Month(s)
Authorisation status: Authorised
ATC code: B01AC06 — ACETYLSALICYLIC ACID
Marketing authorisation: 11063
MA holder: PFIZER AB
MA country: Sweden
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Placebo 1

The placebo tablet composition is: Collodial silicone dioxide, Magnesium stearate, Carmellose sodium, Cellulosa powder. Appearance and size will be the same for active and placebo.

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
Route of administration: ORAL
Max daily dose: 160 mg milligram(s)
Max total dose: 160 mg milligram(s)
Max treatment duration: 36 Month(s)
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation: Karolinska Institutet
Address: Nobels Vag 6
City: Solna
Postcode: 171 65
Country: Sweden

Scientific contact point

Organisation: Karolinska Institutet
Contact name: Anna Martling

Public contact point

Organisation: Karolinska Institutet
Contact name: Anna Martling

Third parties 1

Organisation	City, country	Duties
A+ Science AB ORL-000010973	Stockholm, Sweden	On site monitoring

Locations

4 EU/EEA countries · 33 investigational sites

By country

Country	MS status	Planned subjects	Sites
Denmark	Authorised, recruitment pending	60	3
Finland	Authorised, recruitment pending	100	2
Norway	Authorised, recruitment pending	100	4
Sweden	Authorised, recruitment pending	440	24
Rest of world	—	0	—

Investigational sites

Denmark

3 sites · Authorised, recruitment pending

Regionshospitalet Randers

Surgical Department, Østervangsvej, 54, Randers

Regionshospitalet Viborg

Surgical department, Heibergs Alle 2, 8800, Viborg

Aarhus Universitetshospital

Surgical department, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N

Finland

2 sites · Authorised, recruitment pending

Jorvi Hospital

Surgical department, Turuntie 150, 02740, Espoo

HUS-Yhtymae

Surgical Department, Haartmaninkatu 4, 00290, Helsinki

Norway

4 sites · Authorised, recruitment pending

University Hospital of North Norway

Surgical department, Postboks 100, 9038, Tromsø

St. Olavs Hospital HF

Surgical Department, Prinsesse Kristinas G. 3, 7030, Trondheim

Stavanger HF, Stavanger universitetssykehus

Surgical Department, Jan Johnsensgt 5, 4011, Stavanger

Akershus University Hospital

Surgical department, Sykehusveien 25, 1474, Loerenskog

Sweden

24 sites · Authorised, recruitment pending

Region Oestergoetland

Surgical Department, Universitetssjukhuset I Linkoping, 581 85, Linkoping

NU Hospital Group-Vaestra Goetalandsregionen

Surgical department, Larketorpsvagen, 461 85, Trollhattan

Region Vaestmanland

Surgical department, Centrallasarettet 1, Vasteras Badelunda, Vasteras

Region Skane Lasarettet I Ystad

Surgical Department, Kristianstadsvagen 3, 271 33, Ystad

Capio S:t Goerans Sjukhus AB

Surgical Department, Sankt Goransplan 1, Vastermalm, Stockholm

Danderyds Sjukhus AB

Surgical Department, Morbygardsvagen 88, 182 88, Danderyd

Ersta Sjukhus-Ersta Hospital

Surgical Department, Folkungagatan 125, Sofia, Stockholm

Soedersjukhuset AB

Surgical department, Sjukhusbacken 10, Hogalid, Stockholm

Region Oerebro Laen

Surgical Department, Sodra Grev Rosengatan, 701 85, Orebro

Region Blekinge

Surgical Department, Lasarettsvagen, 371 85, Karlskrona

Region Dalarna

Surgical Department, Vasagatan 27, Falu Kristine, Falun

Uppsala University Hospital

Surgical Department, Akademiska Sjukhuset, 751 85, Uppsala

Region Skane Skanes Universitetssjukhus

Surgical department, Jan Waldenstroms Gata 16 Plan 5, Malmo St Johannes, Malmo

Region Joenkoepings Laen

Surgical Department, Futurum Verksamhetsnara Funktion, Lanssjukhuset Ryhov Hus B 4, Jonkoping

Vrinnevisjukhuset I Norrkoeping Region Oestergoetland

Surgical Department, S Borg, Gamla Ovagen 25, Norrkoping

Skaraborg Hospital-Vaestra Goetalandsregionen

Surgical Department, Lovangsvagen 1, 541 42, Skovde

Sahlgrenska University Hospital-Vaestra Goetalandsregionen

Surgical Department, Diagnosvagen 11, Harlanda, Gothenburg

Region Vaermland

Surgical Departmen, Rosenborgsgatan 50, 652 33, Karlstad

Region Vaesternorrland

Oncological Department, Lasarettsvagen 21, 856 43, Sundsvall

Region Norrbotten

Surgical Department, Robertsviksgatan 7, Lulea Domkyrkofors., Lulea

Karolinska University Hospital

Department of Pelvic Cancer, Eugeniavagen 3, 171 64, Solna