Study evaluating the tailored management of locally-advanced rectal carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Regional Du Cancer De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Feb 2022 → ongoing

Decision date (initial)

2024-04-09

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511609-44-00

EudraCT number

2021-000414-41

ClinicalTrials.gov

NCT04749108

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety

Phase II: To assess, for good responders patients to neoadjuvant CT (NACT), a de-escalation treatment strategy respecting a satisfactory R0 resection rate (90%).
Phase III: To assess for good responders patients to NACT a de-escalation treatment strategy respecting the actual 3 years DFS in a non-inferiority trial.

Secondary objectives 13

1. To estimate the compliance rate of the therapeutic schedule
2. To assess the pathological complete response rate
3. To evaluate the Overall survival
4. To specify the efficiency of MRI (Volume, Down staging-sizing, CRM, NAR:neo adjuvant rectal score [George TJ & al] for prognosis for DFS
5. The Disease Free Survival (For phase III adaptative design)
6. The metastatic recurrence rate - the Disease Free Survival (For
7. To evaluate Safety of the neoadjuvant chemotherapy and radiochemotherapy (arm B)
8. To evaluate the operative morbidity
9. To estimate the sphincter-saving surgery rate
10. To evaluate the post-operative morbidity
11. To evaluate the Functional results (digestive, urinary and sexual functional results)
12. To evaluate the quality of life (QLQ-C30+CR29)
13. To evaluate the Disease Free Survival (For phase III adaptative design)

Conditions and MedDRA coding

Rectum cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patient with tumoral regression ≥ 60% and CRM ≥ 1mm,
2. No unequivocal evidence on CT-Scan of established metastatic disease
3. General condition considered suitable for radical pelvic surgery and a systemic therapy with Capecitabine
4. Adequate hematologic, hepatic, renal and ionogram function assessed within 7 days prior to study treatment

Exclusion criteria 6

1. Patient with a history of pelvic radiotherapy,
2. Contraindication to chemotherapy and/or radiotherapy,
3. Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL),
4. Known hypersensitivity to Capecitabine drug, study drug classes, or any constituent of the products,
5. Pregnant or breastfeeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum β-hCG) documented 72 hours prior to inclusion,
6. Patient treated with an investigational drug within the last 30 days,

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase II : The primary endpoint is the R0 resection rate (R0 is a Circumferential resection margin (CRM) ≥1 mm).
2. Phase III: The primary endpoint is the 3 year-DFS.

Secondary endpoints 18

1. The compliance rate of the therapeutic schedule
2. Sphincter saving surgery rate
3. Pathological complete response rate
4. Dworak Grading
5. Rates of TME grading (Quirke)
6. Distal margin (DM)
7. Neoadjuvant rectal Score
8. 2-3 year Local recurrence rate using the time to local recurrence (TLR) defined as the time interval from the date of randomization to the date of local recurrence. Patients without local recurrence will be censored at the date of last follow-up or death.
9. 2-3 year Metastasis recurrence rate using the time to metastasis defined as the time interval from the date of randomization to the date of metastasis. Patients without metastasis will be censored at the date of last follow-up or death.
10. 3-year local recurrence free survival rate (L-RFS) defined as the time interval from the date of randomization to the date of local recurrence or death from any cause). Patients alive without local recurrence will be censored at the date of last follow-up.
11. 3-year metastasis recurrence free survival rate (M-RFS defined as the time interval from the date of randomization to the date of metastatic recurrence or death from any cause). Patients alive without metastasis will be censored at the date of last follow-up.
12. 3-year disease free survival rate (DFS) defined as the time interval from the date of randomization until the date of the first cancer-related event, or death from any cause). Patients alive without event will be censored at the date of last follow-up.
13. 3 and 5-year Overall survival (OS) defined as the time interval from the date of randomization to the date of death from any cause. Patients alive will be censored at the date of last follow-up.
14. Safety of neoadjuvant chemotherapy and radiochemotherapy will be evaluated using the NCI-CTCAE version 5.0 scale until the end of the post legal surgery period.
15. Operative morbidity: Clavien-Dindo score (3 & 4), definitive stoma rate, second surgery rate, rehospitalization rate.
16. Digestive: LARS syndrome (randomization, post-surgery, 4, , and 12 months after surgery,
17. Urinary and sexual function evaluated by questionnaires at randomization, post-surgery, 4 and 12 months after surgery
18. Quality of life evaluated by the EORTC QLQ-C30 + CR29 questionnaires (randomization, post-surgery, 4 and 12 months after surgery)

Investigational products

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

Test 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Regional Du Cancer De Montpellier

Sponsor organisation

Institut Regional Du Cancer De Montpellier

Address

208 Avenue Des Apothicaires

City

Montpellier Cedex 5

Postcode

34298

Country

France

Scientific contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Pr Philippe Rouanet

Public contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Pr Philippe Rouanet

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 13 files

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

Application history

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