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Locally Advanced Rectal AdenocarcinomaPhase 3NACRE-2NCT07118800

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

A Phase 3 study testing FOLFOX4s and Short Course Radiotherapy in people with Locally Advanced Rectal Adenocarcinoma, run by UNICANCER.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 75 years and older
Conditions the study is for
Locally Advanced Rectal Adenocarcinoma
What is being tested?
FOLFOX4s and Short Course Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
No sites listed yet
Study dates
24 Jul 2026to 15 Jan 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 75 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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
  • Patients must be affiliated to a Social Security System (or equivalent).
  • 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
  • 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.

Who cannot join

  • 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
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  • 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.
  • Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Nicolas DE SOUSA CARVALHO contact

01 71 93 67 09

n-de-sousa@unicancer.fr

About this study

Official title: Randomized Phase III Study Evaluating Two Treatment Strategies for Locally Advanced Rectal Cancer in Patients ≥75 Years Old

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:

Read more
  • 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.

Read the detailed description

Comparative interventional prospective phase III, multicenter, randomised, open-label trial evaluating management strategies of locally advanced rectal cancer treatment with SCRT+/-FOLFOX4s+/-TME to optimize chemotherapy use and increase organ preservation in patients ≥ 75 years

Being tested
FOLFOX4s, Short Course Radiotherapy
Keywords
Locally advanced, Rectum, Resectable, Adenocarcinoma, FOLFOX, Total neoadjuvant treatment, watch and wait, Non operative management, Short Course Radiotherapy
Medical subject headings
Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOX4sDrug

    Also called Chermotherapy, 5FU + Oxaliplatin + folinic acid

    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

  • Short Course RadiotherapyRadiation

    Also called SCRT, Radiotherapy

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

Study groups in NCT07118800
Study groupRoleWhat they receive
Short Course Radiotherapy (SCRT)Active comparatorSCRT 25 Gy in 5 fractions of 5 Gy delivered in one week
Receives: Radiation: Short Course Radiotherapy
Short Course Radiotherapy followed by FOLFOX4sExperimentalSCRT 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.
Receives: Drug: FOLFOX4s; Radiation: Short Course Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Secondary outcomes (14)
  1. Rate of clinical Complete Response

    Defined as the percentage of CR confirmed by central review after 21 weeks divided by the number of patients.

    Measured: 21 weeks

  2. Overall survival

    The overall survival is the length of time from randomization that patients enrolled in the study are still alive.

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

  3. Locoregional failure

    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 and 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.

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

  4. Disease-free survival

    Disease-free survival is defined as the delay between date of inclusion and tumor relapse (local, regional, or distant) or death from any cause, whichever occurs first.

    Measured: 2 years

  5. Regrowth Rate

    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 clinical complete response.

    Measured: 2 years

  6. Metastasis-Free Survival

    The metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body.

    Measured: 2 years

  7. Rate of R0 resection

    Defined as the percentage of R0 resection among patients with TME surgery (for patient with surgery only)

    Measured: 3 years

  8. Rate of postoperative complications of initial surgery

    Define as the percentage of patients having complication using Clavien-Dindo classification after initial surgery divided by the number of patients who undergo initial surgery

    Measured: From initial surgery up to 3 months.

  9. Rate of postoperative complications of salvage surgey after initial non operative management (NOM)

    Define as the percentage of patients having complication using Clavien-Dindo classification after salvage surgery after initial NOM divided by the number of patients who undergo salvage surgery

    Measured: From salvage surgery up to 3 months.

  10. Acute and late toxicity during the study

    The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

    Measured: Throughout study completion, up to 3 years.

  11. Bowel function

    Defined by LARS score

    Measured: At inclusion, 3 months post-radiotherapy, 12 months and 24 months post inclusion.

  12. Quality of life questionnaire - Core 30 (QLQ-C30)

    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

    The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: at inclusion, 3 months post-radiotherapy, 12 months and 24 months post inclusion.

  13. Quality of life questionnaire - Elderly cancer patients (QLQ-ELD14)

    The EORTC QLQ-ELD14, a validated HRQOL questionnaire for cancer patients aged greater than or equal to70 years, is intended to supplement the QLQ-C30.

    The QLQ-ELD14 contains 14 items incorporating five scales to assess mobility, worries about others, future worries, maintaining purpose, and illness burden. In addition, two single items assess joint stiffness and family support. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. High scores indicate poor mobility, good family support, much worry about the future, good maintenance of autonomy and purpose, and high burden of illness.

    Measured: at inclusion, 3 months post-radiotherapy, 12 months and 24 months post inclusion.

  14. Geriatric Core Dataset (G-CODE)

    The G-CODE was developed by the DIalog for personALization of management in geriatric OncoloGy (DIALOG) intergroup to assess the general health status of the older patient.

    The G-Code contains 10 tools incorporating seven scales to assess social environment, functional status, mobility, nutritional status, cognitive status, depressive mood, and comorbidities. The total scale range 0-62. High score indicate better condition.

    Measured: at 3 months post radiotherapy, 12 and 24 months post inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2025
  2. Study start24 Jul 2026 (estimated)
  3. Primary completion15 Dec 2030 (estimated)
  4. Study completion15 Jan 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07118800
Sponsor's protocol ID
UC-GIG-2408
Other IDs
2025-521619-37-00, 2025
Acronym
NACRE-2
Status last verified
Jul 2026
First submitted
5 Aug 2025
Last updated
24 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing FOLFOX4s and Short Course Radiotherapy in people with Locally Advanced Rectal Adenocarcinoma, run by UNICANCER.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nicolas DE SOUSA CARVALHO (01 71 93 67 09, n-de-sousa@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

TME-free survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.

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