Overview
Sponsor-declared trial summary
Cancer(colon cancer stage II-III, rectal cancer, and breast cancer)over-expressing Fascin1
To assess whether treatment with Tofranil© produces significant changes in the histological and molecular manifestations of the epithelial-mesenchymal transition (EMT) in the period from tumor diagnosis by biopsy to surgical resection. The evaluation of the Main Objective will be carried out in the histological examin…
Key facts
- Sponsor
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hormonal diseases [C19], Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 19 Aug 2022 → ongoing
- Decision date (initial)
- 2023-08-07
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-504943-15-00
- EudraCT number
- 2021-001328-17
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To assess whether treatment with Tofranil© produces significant changes in the histological and molecular manifestations of the epithelial-mesenchymal transition (EMT) in the period from tumor diagnosis by biopsy to surgical resection.
The evaluation of the Main Objective will be carried out in the histological examination of the tumor piece product of the surgical resection; usually at 2-6 weeks for group A and between 3-6 months for neoadjuvant patients (group B).
Secondary objectives 1
- To evaluate if the treatment with Tofranil© produces a decrease in the quantification of circulating mutated tumor DNA or in the serum levels of Fascina1. This secondary objective will be evaluated only if the primary objective demonstrates a beneficial effect of Tofranil©.
Conditions and MedDRA coding
Cancer(colon cancer stage II-III, rectal cancer, and breast cancer)over-expressing Fascin1
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10038038 | Rectal cancer | 100000004864 |
| 21.0 | PT | 10009955 | Colon cancer stage III | 100000004864 |
| 20.0 | PT | 10006187 | Breast cancer | 100000004864 |
| 21.0 | PT | 10009954 | Colon cancer stage II | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Resectable tumor.
- Obtaining Written Informed Consent.
- Diagnosis of colon, rectal or triple negative breast cancer by biopsy.
- Overexpression of fascina1 in primary tumor.
- Patient over 18 years of age
Exclusion criteria 10
- Metastatic disease at diagnosis or not candidates for neoadjuvant therapy.
- Colorectal cancer with clinical symptoms of sub-obstruction or obstruction.
- Known diagnosis of major depressive disorder, bipolar depression, or psychosis.
- ECOG scale 3 or 4.
- Severe renal failure (GFR <30 mL/min).
- Hepatic failure or bilirubin > 2 mg/dl.
- Suspected inability to comply with treatment adequately or conditions that limit its reliability (psychiatric illness, drug addiction, etc.).
- History of heart disease.
- Patient on current treatment with SSRIs, SNRIs, MAOIs, tramadol or trazadone or within the 14 days prior to recruitment.
- Woman of childbearing age who refuses to use any contraceptive method.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Changes in the invading front associated with the epithelial-mesenchymal transition quantified as measurement of tumor budding, cytoplasmic pseudofragments, pattern of tumor invasion, and characteristics of the immune infiltrate (intra- and peritumoral lymphocytes, characterization of Crohn-like response macrophages).
Secondary endpoints 1
- Evaluation of plasma quantification of tumor DNA copies and the expression of serum and tissue fascina1 in the surgical resection piece.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
TOFRANIL 50 mg comprimidos recubiertos
PRD791264 · Product
- Active substance
- Imipramine Hydrochloride
- Pharmaceutical form
- COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 195 mg milligram(s)
- Max total dose
- 30745 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- N06AA02 — IMIPRAMINE
- Marketing authorisation
- 48.384
- MA holder
- AMDIPHARM LIMITED
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The Pharmacy Service of the Hospital General Universitario Santa Lucía will be responsible for manufacturing the medication for the trial. The preparation of the trial medication will be carried out by qualified personnel in the pharmacotechnics white room of the Pharmacy Service following the SOP of Annex I, II, III and IV. The goal of this process is to ensure that the dosage form of the investigational drug (IM) is the same as the placebo and that the two are indistinguishable. The MI consists of imipramine capsules of 2 different doses: 25 mg and 65 mg. For the elaboration of the MI, Tofranil® 50mg tablets will be used, which will be disintegrated and encapsulated at a rate of 25 or 65 mg per capsule in each case. The capsules will be manufactured in batches of 200 capsules. In each batch, a mass uniformity quality control will be carried out by weighing and a batch number will be assigned. Regarding the expiration date given to the capsules, an evaluation of the impact that manufacturing and reconditioning could have on the stability of the final preparation has been carried out using the Risk Matrix for Non-Sterile Preparations of the Correct Manufacturing Standards Guide. Medicines for Human and Veterinary Use (Annex V). For the elaboration of the placebo, the same excipients will be encapsulated as in the MI and in the same proportions. Both MI and placebo will be encapsulated in No. 3 hard gelatin capsules. and no. 4 opaque red. The final weight and appearance in both preparations will be the same.
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- 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
Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Sponsor organisation
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Address
- Carretera De Cartagena S/n, El Palmar El Palmar
- City
- Murcia
- Postcode
- 30120
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Contact name
- Clinical trial information desk
Public contact point
- Organisation
- Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia
- Contact name
- Clinical trial information desk
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 180 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
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 |
|---|---|---|---|---|---|
| Spain | 2022-08-19 | 2022-08-19 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | Procedimiento de seleccion de pacientes | 1 |
| Subject information and informed consent form (for publication) | HIPCI HITCLIF HCUVA V1 21052022 HCUVA english | 1 |
| Subject information and informed consent form (for publication) | HIPCI HITCLIF IHQ V2 22062022 | 2.0 |
| Subject information and informed consent form (for publication) | HIPCI HITCLIF IHQ V2 22062022 english | 2.0 |
| Subject information and informed consent form (for publication) | HIPCI HITCLIF V1 del 21052021 | 1 |
| Subject information and informed consent form (for publication) | V5 HIPCI Biobanco Murcia | 5 |
| Subject information and informed consent form (for publication) | V6 HIPCI Biobanco Murcia | 6 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-07-31 | Spain | Acceptable 2023-08-07
|
2023-08-07 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-11-02 | Spain | Acceptable 2024-01-15
|
2024-01-15 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-05-22 | Spain | Acceptable | 2025-06-13 |