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

Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age75+
SponsorUNICANCER

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

  • Short Course Radiotherapy

    Radiation

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

Treatment groups

160 Participants
are divided into 2 treatment groups
Group A: Short Course Radiotherapy (SCRT)Active comparator 1 intervention
Group B: Short Course Radiotherapy followed by FOLFOX4sExperimental treatment 2 interventions

Trial outcomes

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.

Time frame
2 years

Secondary outcomes

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.

Time frame
21 weeks
2

Overall survival

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

Time frame
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.

Time frame
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.

Time frame
2 years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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