Efficacy of the use of neoadjuvant with/without hyperthermic intraperitoneal chemotherapy in the treatment of locally advanced colon cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica De Cordoba

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-08-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Carlos III Health Institute (ISCIII)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine whether the use of proactive systemic neoadjuvant treatment (FOLFOX) with or without HIPEC with mitomycin C followed by post-surgical systemic adjuvant treatment increases disease-free survival at 36 months in patients with locally advanced colon cancer compared to standard treatment.

Secondary objectives 7

1. To conduct a stratified analysis by factors including tumor location (right/left), definitive pathologic stage II/III (high risk), sex and age
2. To evaluate tumor regression after neoadjuvant treatment using the Dworak tumor regression scale (grade 0-no regression to grade 5-total response)
3. To evaluate the R0 surgery rate in the different treatment groups
4. To compare the circulating tumor DNA (ctDNA) detected before and after the treatment in both, experimental and control groups and analyze its impact in survival according to its detection
5. To evaluate the morbidity and toxicity in the different treatment groups
6. To determine the efficacy of neoadjuvant systemic treatment with or without HIPEC association in peritoneal (local or diffuse) recurrence-free survival (PFS) at 36 months
7. To evaluate the effect of neoadjuvant therapy associated with HIPEC compared to neoadjuvant treatment on the pattern of disease recurrence

Conditions and MedDRA coding

Locally advanced adenocarcinoma of the colon and upper rectum with microsatellite stability and with stage cT4N0-2M0 (possible cT3 with pericolic fat penetration > 5mm) by imaging test (CT scan or MRI).

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients of both sexes, aged ≥18 years and ≤75 years
2. Adenocarcinoma of the colon, sigmoid colon and rectum-sigmoid junction that is cT4a/b according to the American Joint Committee on Cancer (AJCC) TNM eigth edition. Pre-treatment diagnosis by imaging test (CT scan or MRI). High-risk cT3 with invasion into surrounding fat greater than 5mm may be included
3. Metastatic extension: M0
4. ECOG 0-1
5. Microsatellite stability (pMMR)
6. Informed consent duly completed
7. Subjects must agree to utilize a highly effective* method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study (*) Highly effective methods of contraception as defined by the Clinical Trial Facilitation Group (CTFG) (“Recommendations related to contraception and pregnancy testing in clinical trials”, version 15/09/2014) o Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) o Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) o Intrauterine device (IUD) o Intrauterine hormone-releasing system (IUS) o Bilateral tubal occlusion o Vasectomised partner o Sexual abstinence

Exclusion criteria 11

1. Presence of metastases (M1). If liver or peritoneal metastases are present at the time of surgery, the patient will be excluded from the study and treated according to the new stage
2. Presence of un-resectability criteria in the pretreatment work-up, un-resectability will be discussed in MDT with expert oncologic surgeons.
3. Presence of microsatellite instability (dMMR)
4. Presence of deficit of DPD.
5. Coexistence of another malignant neoplastic disease (synchronous colon and rectum-sigmoid tumors are accepted as long as the stage is equal or lower than the treated tumor)
6. Extraperitoneal rectal cancer (medium-low) (avoiding alterations due to neoadjuvant radiotherapy).
7. Coexistence of another malignant neoplastic disease (synchronous colon and rectum-sigmoid tumors are accepted as long as the stage is equal or lower than the treated tumor).
8. Severely impaired hepatic, renal or cardiovascular function.
9. Contraindications to study IMPs (annex I) as per investigator criteria
10. Intolerance to treatment. Hypersensitivity to Mitomycin C, Fluoropyrimidine or oxaliplatin. This means individuals with a history of allergic or other adverse reactions to a these specific drugs or their related substances are excluded from participating.
11. Gestational or lactating women. If female and of childbearing potential, must: - Have a negative pregnancy test ≤72hours prior to initiating study treatment - Agree to avoid pregnancy during and for 6 months after study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. disease-free survival (DFS; absolute DFS in months)
2. Probability of DFS at 3 years (DFS 3y%)

Secondary endpoints 8

1. Overall survival: absolute and probability at 3 years
2. Peritoneal recurrence-free survival: absolute and probability at 3 years
3. Pattern of recurrence (peritoneal, hematogenous or lymphatic)
4. Tumor regression grade (Dworak scale)
5. Morbidity and toxicity: Clavien Dindo classification and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 will be considered.
6. Negative rate of ctDNA after treatment and association of detected levels with tumor recurrence and survival
7. Survival analysis in the following subgroups: pT4a/b, pN+, pathologic stage II/III, mutated RAS/RAF, positive/negative ctDNA
8. Tumour progression defined as per RECIST v.1.1: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Investigational products

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

Test 4

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica De Cordoba

Sponsor organisation

Fundacion Para La Investigacion Biomedica De Cordoba

Address

Avenida Menendez Pidal S/n

City

Cordoba

Postcode

14004

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica De Cordoba

Contact name

Alvaro Arjona

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica De Cordoba

Contact name

Jose Carlos Garrido Gracia

Third parties 1

Locations

1 EU/EEA country · 23 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications