Study evaluating two treatment strategies for rectal cancer in patients ≥75 years old

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-02-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCa

External identifiers

EU CT number

2025-521619-37-00

ClinicalTrials.gov

NCT07118800

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To compare efficacy of SCRT followed by 6 cycles of FOLFOX4s chemotherapy versus SCRT without chemotherapy in terms of organ preservation rate in elderly patients with locally advanced rectal cancer (cT3-T4).

Secondary objectives 13

1. To compare between the two arms in terms of Rate of clinical Complete Response (cCR) at 21 weeks
2. To compare between the two arms in terms of 24-months Overall survival (OS)
3. To compare between the two arms in terms of Rate of Locoregional-free survival (LRFS) at 24 months
4. To compare between the two arms in terms of 24-months Disease-free survival (DFS)
5. To compare between the two arms in terms of 24-months Local Regrowth Rate
6. To compare between the two arms in terms of 24-months Metastasis-free survival (MFS)
7. To compare between the two arms in terms of Rate of R0 resection
8. To compare between the two arms in terms of Rate of postoperative complications of initial surgery at 3 months
9. To compare between the two arms in terms of Rate of postoperative complications of salvage surgery after initial NOM at 3 months
10. To compare between the two arms in terms of Safety profile
11. To compare between the two arms in terms of Bowel dysfunction at inclusion, 3 months post-radiotherapy, 12 months and 24 months post inclusion
12. To compare between the two arms in terms of Quality of life (QoL) at inclusion, 3 months post-radiotherapy, 12 months and 24 months post inclusion
13. To compare between the two arms in terms of Geriatric evaluation, at inclusion, 3 months post-radiotherapy, 12 months and 24 months post inclusion.

Conditions and MedDRA coding

Patients ≥75 years old with cT3/T4 rectal adenocarcinoma eligible to radiotherapy, FOLFOX chemotherapy and total mesorectal excision (TME) surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Histologically confirmed diagnosis of adenocarcinoma of the rectum
2. Age ≥75 years
3. WHO performance status 0-1
4. cT3a-b with maximum diameter > 5 cm, T3c-d or cT4 tumor on pretreatment pelvic MRI
5. General condition considered suitable for radical pelvic surgery and a systemic therapy with FOLFOX,
6. Distal part of the tumor ≤10 cm from the anal margin, the measurement done by pelvic MRI
7. Oncogeriatrician approval
8. Adequate biological function defined by: a. Neutrophils ≥ 1500/mm3 b. Platelets ≥ 100 000/mm3 c. Hemoglobin ≥ 10g/dL d. Total bilirubin ≤ 1,5 x ULN e. Alkaline phosphatases ≤ 1,5 x ULN f. Creatinine clearance >50mL/mn (MDRD) g.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels 2.5× ULN
9. Men must agree to use adequate contraception methods during treatment and at least until 12 months after the end of the treatment with oxaliplatin
10. Patients must be affiliated to a Social Security System (or equivalent).
11. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent
12. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion criteria 17

1. Metastatic disease
2. Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders).
3. Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
4. Any psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
5. No prior chemotherapy or surgery for rectal cancer
6. Any serious underlying medical condition (as judged by the investigator) that could impair the ability of the patient to participate in the trial
7. Persons deprived of their liberty or under protective custody or guardianship.
8. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
9. Other cancer within 3 years prior to rectal cancer diagnosis (except for in situ cancer and basal cell carcinoma of the skin)
10. Non resectable cancer, including extension to prostate or extension to perineal muscles
11. History of pelvic irradiation
12. Contraindication to FOLFOX 4s chemotherapy: Regarding the treatment with 5-fluorouracil: ➢ Recent (within the last 4 weeks) or concomitant treatment with brivudine ➢ Presence of a potentially serious infection Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose of the study intervention ➢ Poor nutritional status/Clinically significant active heart disease or myocardial infarction within the past 6 months, given the cardiotoxicity of fluorouracil. Regarding the treatment with oxaliplatin: Due to the cardiotoxicity of oxaliplatin (risk of QT prolongation as described in section 4.4 of the oxaliplatin SmPC): ➢ hypokalemia less than normal ➢ hypomagnesemia ➢ hypocalcemia ➢ QT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG; Peripheral sensory neuropathy with functional impairment prior to the first treatment, according to the oxaliplatin SmPC. Known history of hypersensitivity to fluorouracil, oxaliplatin, folinic acid, or any of their excipients, as stated in the respective SmPCs.
13. Contraindication to MRI
14. Microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR)
15. Complete or partial Dihydropyrimidine Deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
16. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment
17. Contradiction radiotherapy and/or TME surgery

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The 24-months TME-free survival will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval. Organ preservation rate at 24 months, defined as proportion of patients without TME, or nonsalvageable pelvic disease, and without permanent diversion stoma. Patients alive at the time of analysis or lost from follow-up will be censored at the date of the latest news.

Secondary endpoints 13

1. Rate of cCR will be defined as percentage of CR confirmed by central review after 21 weeks divided by the number of patients. CR is defined as flat, white scar, with telangiectasia, no ulcer or nodularity on endoscopic evaluation, no induration on digital rectal examination, normal appearing bowel wall without any fibrosis in the tumor bed, dark T2 signal, no mesorectal lymph node on pelvic MRI-T2W, no visible signal on B800-B1000 MRI-DW, no metastatic dissemination on chest, abdominal CT scan
2. The 24-month overall survival defined as the period between the date of randomization and the date of death related to the cancer. Patients who did not die at the time of analysis or are lost-of-follow-up will be censored at the date of the latest news. The 24-months OS will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval.
3. Locoregional failure at 24 months, defined as either an unresectable rectal primary tumor following protocol neoadjuvant treatment, an R2 resection for the rectal primary tumor, or recurrence in the primary tumor bed after an R0-R1 resection. Tumor regrowth in the rectal wall or in regional lymph nodes after a cCR or near-complete response, a period of Watch & Wait or after local scar excision (for ypT0 and T1 tumor) will not be considered a locoregional failure if followed by an R0-R1 resection
4. The 24-months disease-free survival defined as the period between the date of randomization and the date of locoregional failure (as described above), distant metastasis, a new invasive colorectal primary cancer, or death from any cause. The 24-months DFS will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval.
5. 24-month Regrowth Rate will be defined as the proportion of patients presenting tumor regrowth during their surveillance in the “watch and wait” strategy or after local scar excision after they achieved cCR.
6. The 24-month metastasis-free survival will be defined as the period between the date of randomization and the date of detection of distant metastasis. The 24-months MFS will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval.
7. Rate of R0 resection will be defined as the percentage of R0 resection among patients with TME surgery (for patient with surgery only)
8. Rate of postoperative complications of initial surgery will be assessed at 3 months using Clavien-Dindo classification (for patient with surgery only)
9. Rate of postoperative complications of salvage surgery after initial NOM will be assessed at 3 months using Clavien-Dindo classification (for patient with surgery only)
10. The safety profile in each arm will be described using the common toxicity criteria from the CTCAE v5.0.
11. The Bowel function will be assessed using the LARS score at inclusion, 3 months postradiotherapy, 12 months and 24 months post inclusion.
12. Quality of life will be assessed by QLQ-C30 and ELD-14 score at inclusion, 3 months postradiotherapy, 12 months and 24 months post inclusion.
13. Geriatric assessment will be evaluated using G8, MMS, ADL, IADL, TUG, Charlson, ACE 27, SARC F, Hand grip, 5-time chair, G Code at inclusion, then G Code at 3 months post radiotherapy, 12 and 24 months post inclusion

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 22 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 12 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