Study Evaluating Two Treatment Strategies for Rectal Cancer in Patients ≥75 Years Old

NCT07118800 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: UC-GIG-24082025-521619-37-00
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the NACRE-2 trial is to assess whether the addition of chemotherapy after short-course radiotherapy is more effective than short-course radiotherapy alone in elderly patients with locally advanced rectal cancer. Secondary objectives will assess the efficacy and safety profile of the combination, as well as its effect on patients' quality of life. Patients will be separated into two groups to receive their assigned treatment:

• Group 1: Short-duration radiotherapy according to standard practice lasting one week, followed by chemotherapy with FOLFOX4s consisting of oxaliplatin (85 mg/m²), folinic acid (400 mg/m²) and 5-Fluoro-Uracil (400 mg/m² administered in hospital, followed by 2400 mg/m² administered over 46 hours at home) every two weeks for 3 months
• Group 2: Short-duration radiotherapy according to standard practice, lasting one week To receive treatment, patients must come to the hospital where, at each visit, the medical team will carry out medical examinations, prior to administering treatment, to assess the patient's general state of health and tolerance to treatment. A radiological assessment of the disease will be carried out 11 weeks after the end of radiotherapy. Patients whose tumors have not shrunk will undergo surgery to remove them and enter the follow-up phase. Patients whose tumors have shrunk will not undergo surgery, and will enter a surveillance phase. At 21 weeks, patients whose tumors are still present will undergo surgery and enter the follow-up phase. Patients whose tumors have disappeared will remain in a surveillance phase. During the surveillance or follow-up phases, patients will be monitored in hospital every 3 months (if no progression is observed). In the case of surgery, patients will be monitored every 6 months. The maximum duration of treatment is 3 years.

Conditions

Locally Advanced Rectal Adenocarcinoma

Keywords

Locally advanced; Rectum; Resectable; Adenocarcinoma; FOLFOX; Total neoadjuvant treatment; watch and wait; Non operative management; Short Course Radiotherapy

Outcome Measures

Primary Outcomes (1)

• TME-free survival

  defined as proportion of patients without TME, or non-salvageable 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.

  2 years

Secondary Outcomes (14)

• Rate of clinical Complete Response

  21 weeks

• Overall survival

  From randomization to death from any cause, up to 2 years.

• Locoregional failure

  Time from randomization to locoregional failure, up to 2 years.

• Disease-free survival

  2 years

• Regrowth Rate

  2 years

Study Arms (2)

Short Course Radiotherapy (SCRT)

ACTIVE COMPARATOR

SCRT 25 Gy in 5 fractions of 5 Gy delivered in one week

Radiation: Short Course Radiotherapy

Short Course Radiotherapy followed by FOLFOX4s

EXPERIMENTAL

SCRT 25Gy in 5 fractions of 5Gy delivered in one week followed by 6 cycles of FOLFOX4s intravenously: Oxaliplatin 85mg/m² over 2h, folinic acid 400mg/m2 (or L-folinic acid 200 mg/m2) over 2h, Fluorouracil "bolus" 400mg/m², Fluorouracil: 2400mg/m² over 46h, every 14 days for 12 weeks (max: 6 cycles). FOLFOX4s regimen will be started 2-4 weeks after completion of radiotherapy.

Drug: FOLFOX4s; Radiation: Short Course Radiotherapy

Interventions

FOLFOX4s DRUG

6 cycles of FOLFOX4s intravenously: Oxaliplatin 85mg/m² over 2h, folinic acid 400mg/m2 (or L-folinic acid 200 mg/m2) over 2h, Fluorouracil "bolus" 400mg/m², Fluorouracil: 2400mg/m² over 46h, every 14 days for 12 weeks (max: 6 cycles). FOLFOX4 regimen will be started 2-4 weeks after completion of radiotherapy

Also known as: Chermotherapy, 5FU + Oxaliplatin + folinic acid

Short Course Radiotherapy followed by FOLFOX4s

Short Course Radiotherapy RADIATION

25Gy in 5 fractions of 5Gy delivered in one week (short-course radiotherapy)

Also known as: SCRT, Radiotherapy

Short Course Radiotherapy (SCRT); Short Course Radiotherapy followed by FOLFOX4s

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of adenocarcinoma of the rectum
• Age ≥75 years
• WHO performance status 0-1
• cT3a-b with maximum diameter \> 5 cm, T3c-d or cT4 tumor on pretreatment pelvic MRI
• General condition considered suitable for radical pelvic surgery and a systemic therapy with FOLFOX,
• Distal part of the tumor ≤10 cm from the anal margin, the measurement done by pelvic MRI
• Oncogeriatrician approval
• Adequate biological function defined by:
• Neutrophils ≥ 1500/mm3
• Platelets ≥ 100 000/mm3
• Hemoglobin ≥ 10g/dL
• Total bilirubin ≤ 1,5 x ULN
• Alkaline phosphatases ≤ 1,5 x ULN
• Creatinine clearance \>50mL/mn (MDRD)
• Men must agree to use adequate contraception methods for the duration of study treatment and for within 6 months after completing treatment

You may not qualify if:

• Metastatic disease
• Other cancer within 3 years prior to rectal cancer diagnosis (except for in situ cancer and basal cell carcinoma of the skin)
• Non resectable cancer, including extension to prostate or extension to perineal muscles
• History of pelvic irradiation
• Contraindication to FOLFOX 4s chemotherapy and/or radiotherapy and/or TME surgery
• Contraindication to MRI
• Microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR)
• Complete or partial Dihydropyrimidine Deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
• 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
• 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).
• Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
• Any psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
• No prior chemotherapy or surgery for rectal cancer
• Any serious underlying medical condition (as judged by the investigator) that could impair the ability of the patient to participate in the trial
• Persons deprived of their liberty or under protective custody or guardianship.

Sponsors & Collaborators

• UNICANCER: lead

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Fluorouracil; Oxaliplatin; Leucovorin; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Therapeutics

Study Officials

• Ludovic EVESQUE

  Centre Antoine Lacassagne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas DE SOUSA CARVALHO

CONTACT

01 71 93 67 09; n-de-sousa@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: August 12, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): December 15, 2030
• Study Completion (Estimated): January 15, 2032
• Last Updated: August 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share