Overview
Sponsor-declared trial summary
Phase
Phase II and Phase III (Integrated)
Status
Ongoing, recruiting
Participants planned
340
Countries
1
Sites
29
Locally advanced stage II/III rectal cancer
Primary objective is to assess the effect of each of the 3 experimental interventions (aspirin, metformin or both, in combination with neoadjuvant induction chemotherapy (ICT) and preoperative chemoradiation (CRT)) compared to standard neoadjuvant ICT followed by preoperative CRT on Good Pathological Response (GPR) def…
Key facts
- Sponsor
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 22 Oct 2020 → ongoing
- Decision date (initial)
- 2025-01-10
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-519007-10-00
- EudraCT number
- 2018-004385-34
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
Primary objective is to assess the effect of each of the 3 experimental interventions (aspirin, metformin or both, in combination with neoadjuvant induction chemotherapy (ICT) and preoperative chemoradiation (CRT)) compared to standard neoadjuvant ICT followed by preoperative CRT on Good Pathological Response (GPR) defined as Tumour downstaging (ypT0 or ypT1) irrespective of the pathological N stage.
Secondary objectives 1
- The secondary objectives are to assess the effect of the experimental interventions compared to the standard neoadjuvant treatment with ICT followed by CRT on: Tumour Regression Grade (TRG) Pathological complete responses (pCR) Neo-Adjuvant Rectal (NAR) score MRI Tumour Downstaging (mr TGR) rate Event-Free Survival (EFS) Overall Survival (OS) Time to Distant Recurrence (TDR) Rate of local recurrence at 3 years Abdominal Perineal Resection (APR) rate Organ preservation rate at 3 years Post-operative complications Quality of Life (QoL) Treatment related toxicity Simplified-ESMO class risk shift after induction chemotherapy
Conditions and MedDRA coding
Locally advanced stage II/III rectal cancer
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Pathologically proven diagnosis of adenocarcinoma of the rectum by endoscopic biopsy within 56 days prior to randomisation. Locally advanced tumour (defined as TNM Stage II or III) based upon the following minimum diagnostic workup: MRI of the pelvis, contrast-enhanced CT of abdomen and chest. Able to undergo induction chemotherapy, chemoradiotherapy and total mesorectal excision (TME). For further information please refer to the protocol
Exclusion criteria 1
- Prior treatment for LARC (recurrent rectal tumours are excluded) or previous pelvic radiotherapy. Unequivocal evidence of established metastatic disease based on minimum diagnostic workup. Patients with equivocal lesions are eligible. Patients already taking daily aspirin and/or metformin for more than 4 weeks prior to randomisation. Hypersensitivity to salicylic acid compounds or prostaglandin synthetase inhibitors and to any of the excipients. Hypersensitivity to metformin or to any of the excipients. For further information please see protocol
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Good Pathological Response (GPR) defined as Tumour downstaging (ypT0 or ypT1) irrespective of the pathological N stage
Secondary endpoints 1
- Tumor Regression Rate Pathological complete responses (pCR) NeoAdjuvant Rectal (NAR) score MRI Tumor Downstaging (mr TGR) rate Event-Free Survival (EFS) Overall Survival (OS) Time to Distant Recurrence (TDR) Rate of local recurrence at 3 years Abdominal Perineal Resection (APR) rate Organ preservation rate at 3 years Post-operative complications Treatment-related toxicity Quality of Life (QoL). For further information please see protocol
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SCP10310250 · ATC
- Active substance
- Metformin Embonate
- Substance synonyms
- Metformin hemiembonate, METFORMIN PAMOATE
- Route of administration
- ORAL USE
- Max daily dose
- 1700 mg milligram(s)
- Max total dose
- 285600 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP131039 · ATC
- Active substance
- Carbasalate Calcium
- Substance synonyms
- Carbaspirin calcium
- Route of administration
- ORAL USE
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 16800 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AC06 — ACETYLSALICYLIC ACID
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 2
SCP128961 · ATC
- Active substance
- Oxaliplatin
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 130 mg/m2 milligram(s)/sq. meter
- Max total dose
- 21840 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP131876 · ATC
- Active substance
- Capecitabine
- Route of administration
- ORAL USE
- Max daily dose
- 2000 mg milligram(s)
- Max total dose
- 336000 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Sponsor organisation
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Address
- Via Mariano Semmola 52
- City
- Naples
- Postcode
- 80131
- Country
- Italy
Scientific contact point
- Organisation
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Contact name
- Maria Carmela Piccirillo
Public contact point
- Organisation
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Contact name
- Maria Carmela Piccirillo
Locations
1 EU/EEA country · 29 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 340 | 29 |
| Rest of world | — | 0 | — |
Investigational sites
Istituto Oncologico Veneto
U. O. di Oncologia Medica 1, Via Gattamelata 64, 35128, Padova
Azienda Ospedaliero-Universitaria Maggiore Della Carita
SCDU Oncologia - AOU Maggiore della Carità - Novara, Corso Giuseppe Mazzini 18, 28100, Novara
Ospedale S G Moscati
Oncologia, Via Per Martina Franca, 74010, Statte
Fondazione IRCCS Istituto Nazionale Dei Tumori
Tumori ereditari dell'apparato digerente, Via Giacomo Venezian 1, 20133, Milan
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
UO Chirurgia tratto alimentare e urgenza, Via Pietro Albertoni 15, 40138, Bologna
Azienda Sanitaria Locale Della Provincia Di Biella
SC Oncologia, Via Dei Ponderanesi 2, 13875, Ponderano
Azienda Ospedaliero Universitaria Di Modena
SSD DH Oncologico Policlinico di Modena -AOU Modena, Largo Del Pozzo 71, 41124, Modena
Istituto Tumori Bari Giovanni Paolo II
Chirurgia Generale, Viale Orazio Flacco 65, 70124, Bari
Ospedale San Giovanni Bosco
SC Oncologia Medica, Piazza Del Donatore Di Sangue 3, 10154, Turin
Centro Di Riferimento Oncologico Di Aviano
SOC Oncologia Medica e Prevenzione Oncologica, Via Franco Gallini 2, 33081, Aviano
Azienda USL IRCCS Di Reggio Emilia
Oncologia Medica, A.U.S.L. di Reggio Emilia - IRCCS - Presidio Arcispedale S. Maria Nuova, Viale Risorgimento 80, 42123, Reggio Emilia
Sant Andrea Hospital
Oncologia, Via Vittorio Veneto 197, 19124, La Spezia
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
SCDU Chirurgia Generale, Regione Gonzole 10, 10043, Orbassano
Azienda Sanitaria Locale TO3
Chirugia Generale Ospedale Agnelli, Via Brigata Cagliari N. 39, 10064, Pinerolo
IRCCS Istituto Nazionale Tumori Fondazione Pascale
UOC Oncologia Chirurgica Colorettale, Via Mariano Semmola 52, 80131, Naples
Azienda Socio Sanitaria Territoriale Di Bergamo Ovest
U.O. Oncologia Medica Osp. Treviglio, Piazzale Ospedale Luigi Meneguzzo 1, 24047, Treviglio
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOC Servizio di Radioterapia Oncologica Gemelli, Largo Francesco Vito 1, 00168, Rome
Azienda Socio Sanitaria Territoriale Della Valtellina E Dell Alto Lario
Oncologia Medica - Ospedale di Sondrio, Via Stelvio N 25, 23100, Sondrio
Ospedale ' Civile Maria Paterno' Arezzo
Oncologia Medica P.O. Maria Paternò Arezzo dell’ASP di Ragusa, Contrada Rito, 97100, Ragusa
Ospedale San Raffaele S.r.l.
Chirurgia gastro-enterologica, Via Olgettina 60, 20132, Milan
Casa Di Cura Macchiarella S.p.A.
Oncologia Medica, Viale Regina Margherita 25, 90138, Palermo
Ospedale Isola Tiberina Gemelli Isola
UOC di Oncologia, Via Di Ponte Quattro Capi 39, 00186, Rome
Azienda Ospedaliera Regionale San Carlo
Unità Operativa di Oncologia Medica - Azienda Ospedaliera S.Carlo, Via Potito Petrone, 85100, Potenza
IRCCS Istituto Nazionale Tumori Fondazione Pascale
SSD Chirurgia robotica addominale_, Via Mariano Semmola 52, 80131, Naples
Azienda Ospedaliero-Universitaria Di Cagliari
Oncologia Medica -AOU Cagliari - Policlinico Universitario "Duilio Casula Monserrato", Strada Statale 554 N. 1, 09042, Monserrato
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Oncologia Medica IRCCS Ca' Granda Osp. Maggiore, Via Francesco Sforza 28, 20122, Milan
Ospedale San Vincenzo Taormina
Oncologia Medica, Contrada Sirina, 98039, Taormina (Italy)
Ospedale Santa Maria della Misericordia
Dipartimento di Oncologia - ASU FC S. Maria della Misericordia -Udine, Piazzale Santa Maria della Misericordia, 15, Udine
Fondazione IRCCS San Gerardo Dei Tintori
Oncologia Medica, Via Giovanni Battista Pergolesi 33, 20900, Monza
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2020-10-22 | 2021-02-11 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocol NeoAspMet v 1 1 del 29 06 2020 for publication | 1.1 |
| Recruitment arrangements (for publication) | blank document | 1 |
| Subject information and informed consent form (for publication) | Consenso tratt dati pers NeoAspMet vers 1 del 7 10 2024 for publication | 1 |
| Subject information and informed consent form (for publication) | Diario Neoaspmet v 1 1 | 1.1 |
| Subject information and informed consent form (for publication) | Informativa e consenso NeoAspMet vers 1 del 29 06 2020 | 1 |
| Subject information and informed consent form (for publication) | Lettera medico di base NeoAspMet vers 1 del 29 06 2020 | 1 |
| Subject information and informed consent form (for publication) | Questionario QoL EORTC C30 CR29 | 0 |
| Summary of Product Characteristics (SmPC) (for publication) | RCP Acido Acetilsalicilico | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | RCP capecitabina | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | RCP metformina | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | RCP oxaliplatino | 1 |
| Synopsis of the protocol (for publication) | Sinossi NeoAspMet vers 0 del 15 11 2018 for publication | 0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-11-29 | Italy | Acceptable 2024-12-20
|
2025-01-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-30 | Italy | Acceptable | 2025-06-18 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-11-12 | Italy | Acceptable | 2025-12-05 |