Efficacy and Safety of Conventional Neoadjuvant Therapy Versus Total Neoadjuvant Therapy in Older Patients With Locally Advanced Rectal Cancer (SHAPERS)

November 28, 2025 updated by: Jules Bordet Institute

Efficacy and Safety of Conventional Neoadjuvant Therapy Versus Total Neoadjuvant Therapy in Older Patients With Locally Advanced Rectal Cancer: a Multicentre, Open-label, Randomised Pragmatic Clinical Trial

The SHAPERS study is a multicentre, open-label, randomised, pragmatic clinical trial, comparing standard-of-care neoadjuvant treatment options for older (i.e., ≥70 years) subjects with high-risk stage II and stage III rectal cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The SHAPERS study is a multicentre, open-label, randomised, pragmatic clinical trial, comparing standard-of-care neoadjuvant treatment options for older (i.e., ≥70 years) subjects with high-risk stage II and stage III rectal cancer.

Subjects meeting all eligibility criteria will be randomised in a 1:1 ratio to either the conventional arm or the TNT arm (The study design is shown in figure 3.1 and 3.2).

Conventional arm consists of:

  • SCRT (5 fractions of 5 Gy), followed by
  • Surgery (according to the principles of TME) or watch & wait, followed by
  • Optional adjuvant chemotherapy OR
  • LCCRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine) followed by
  • Surgery (according to the principles of TME) or watch & wait, followed by
  • Optional adjuvant chemotherapy

TNT arm Different treatment regimens can be used in the TNT arm including Rapido, Rapido light, OPRA INCT-CRT or OPRA CRT-CNCT. The regimen to use will be decided by the investigator and will need to be declared before randomisation. No switch between regimens is allowed during the study treatment period.

The Rapido regimen consists of:

  • SCRT (5 fractions of 5 Gy), followed by
  • Up to 18 weeks of oxaliplatin based chemotherapy (mFOLFOX6 or CAPOX), followed by
  • Surgery (according to the principle of TME) or "watch & wait".

The Rapido light regimen consists of:

  • SCRT (5 fractions of 5 Gy), followed by
  • Up to 12 weeks of oxaliplatin based chemotherapy (mFOLFOX6 or CAPOX), followed by
  • Surgery (according to the principle of TME) or "watch & wait".

The OPRA with induction chemotherapy (INCT-CRT) regimen, consists of:

  • Up to 16 weeks of oxaliplatin-based chemotherapy (mFOLFOX6 or CAPOX), followed by
  • CRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine) followed by
  • Surgery (according to the principle of TME) or "watch & wait"

The OPRA with consolidation chemotherapy (CRT-CNCT) regimen consists of:

  • CRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine) followed by
  • Up to 16 weeks of oxaliplatin-based chemotherapy (mFOLFOX6 or CAPOX), followed by
  • Surgery (according to the principle of TME) or "watch & wait".

Study Type

Interventional

Enrollment (Estimated)

230

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
    • Antwerpen
      • Antwerp, Antwerpen, Belgium, 2610
        • Recruiting
        • ZAS Antwerpen
        • Contact:
        • Principal Investigator:
          • Ines Joye, MD
      • Edegem, Antwerpen, Belgium, 2650
        • Recruiting
        • UZA Antwerpen
        • Principal Investigator:
          • Timon Vandamme, MD
        • Contact:
      • Turnhout, Antwerpen, Belgium, 2300
    • Brussels Capital
      • Anderlecht, Brussels Capital, Belgium, 1070
        • Recruiting
        • Institut Jules Bordet
        • Contact:
        • Principal Investigator:
          • Rita Saude Conde, MD
      • Auderghem, Brussels Capital, Belgium, 1160
      • Brussels, Brussels Capital, Belgium, 1000
      • Brussels, Brussels Capital, Belgium, 1020
    • East Flanders
      • Ghent, East Flanders, Belgium, 9000
        • Recruiting
        • UZ Gent
        • Principal Investigator:
          • Karen Geboes, MD
        • Contact:
      • Sint-Niklaas, East Flanders, Belgium, 9100
        • Recruiting
        • AZ Nikolaas
        • Principal Investigator:
          • Willem Lybaert, MD
        • Contact:
    • Hainaut
      • Haine-Saint-Paul, Hainaut, Belgium, 7100
        • Recruiting
        • Hôpital de Jolimont
        • Contact:
        • Principal Investigator:
          • Alexandre Dermine, MD
      • Hornu, Hainaut, Belgium, 7301
      • Mons, Hainaut, Belgium, 7000
        • Not yet recruiting
        • CHU Ambroise Pare
        • Principal Investigator:
          • Marie Diaz, MD
        • Contact:
    • Liège
      • Liège, Liège, Belgium, 4000
        • Recruiting
        • CHU de Liege - Sart Tilman
        • Contact:
        • Principal Investigator:
          • Elodie GONNE, MD
    • Luxemburg
      • Libramont, Luxemburg, Belgium, 6800
        • Recruiting
        • CHA Libramont
        • Principal Investigator:
          • Frederic Forget, MD
        • Contact:
    • Namur
      • Charleroi, Namur, Belgium, 6042
        • Not yet recruiting
        • CHU Charleroi
        • Contact:
        • Principal Investigator:
          • Angélique Covas, MD
      • Charleroi, Namur, Belgium, 6000
        • Suspended
        • Grand Hopital De Charleroi
      • Godinne, Namur, Belgium, 5530
      • Namur, Namur, Belgium, 5000
        • Not yet recruiting
        • CHR Sambre et Meuse (site Meuse)
        • Contact:
        • Principal Investigator:
          • Yeter Gokburun, MD
      • Namur, Namur, Belgium, 5000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 70 years old

  2. ECOG performance status (PS):

    • ≤1 if age > 75 years old
    • ≤2 if age ≤ 75 years old
  3. Histologically or cytologically confirmed adenocarcinoma of the rectum
  4. Distal border of the tumour below the peritoneal reflection and within 15 cm of the anal verge
  5. Operable stage III or high-risk stage II rectal cancer (high-risk tumours defined as those having ≥1 of the following features: T4, mesorectal fascia (MRF) involvement/threatening [i.e.,tumour within 1 mm of the MRF], extramural venous invasion). Patient with involvement of lateral pelvic lymph nodes are also eligible.

  6. Adequate bone marrow function as defined below:

    • Absolute neutrophil count ≥1,500/µL
    • Haemoglobin ≥9 g/dL
    • Platelets ≥100,000/µL

  7. Adequate liver function as defined below:

    • Serum total bilirubin ≤1.5 x ULN. In case of known Gilbert's syndrome <3xUNL is allowed
    • AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
    • Alkaline phosphatase ≤2.5 x ULN
  8. Adequate renal function as defined by estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73m² (according to the CKD-EPI 2021 equation).
  9. Absence of clinical conditions that in the opinion of the investigator, would contraindicate neoadjuvant therapy and/or surgery.
  10. Signed Informed Consent form (ICF) obtained prior to any study related procedure.
  11. Male subjects with partners of childbearing potential must agree to use condom during the course of this study and for at least 6 months after the last administration of study drugs.

Exclusion Criteria:

  1. Extensive growth into cranial part of the sacrum (above S2/3 junction) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is achieved.
  2. Presence of metastatic disease or recurrent rectal tumour.
  3. Presence of grade ≥2 peripheral neuropathy according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0.
  4. Significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
  5. Any contraindication to pelvic irradiation as evaluated by the investigator.
  6. Known hypersensitivity reactions to the study drugs or to any excipients, premedications or non-investigational medicinal products or concomitant medications.
  7. Any investigational anti-cancer therapy other than the protocol specified therapies (participation in other prospective studies which do not imply any specific intervention may be allowed after discussion with the Study Chair).
  8. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment.
  9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (grade III or IV as classified by the New York Heart Association), or serious cardiac arrhythmia requiring medication within the past 6 months.
  10. Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
  11. Any previous treatment for rectal cancer.
  12. Use of brivudine, sorivudine or their chemically related analogues.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: TNT arm

Rapido regimen:

  • SCRT (5 fractions of 5 Gy)
  • Up to 18 weeks of oxaliplatin based chemotherapy (mFOLFOX6 or CAPOX)
  • Surgery (according to the principle of TME) or "watch & wait"

Or

Rapido light regimen:

  • SCRT
  • Up to 12 weeks of oxaliplatin based chemotherapy
  • Surgery or "watch & wait"

Or

OPRA with induction chemotherapy (INCT-CRT) regimen:

  • Up to 16 weeks of oxaliplatin-based chemotherapy
  • CRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine)
  • Surgery or "watch & wait"

Or

OPRA with consolidation chemotherapy (CRT-CNCT) regimen:

  • CRT
  • Up to 16 weeks of oxaliplatin-based chemotherapy
  • Surgery or "watch & wait"
Procedure: Total mesorectal excision
Surgery must be performed according to the principles of total mesorectal excision. A "watch & wait" approach is allowed for those subjects who have clinical complete response according to the local assessment.
Combination product: Total neoadjuvant therapy

The choice of the TNT is left to the investigator's discretion.

If RAPIDO:

  • SCRT (5 fractions of 5 Gy), followed by
  • Up to 18 weeks of oxaliplatin based chemotherapy (mFOLFOX6 or CAPOX)

If RAPIDO light:

  • SCRT (5 fractions of 5 Gy), followed by
  • Up to 12 weeks of oxaliplatin based chemotherapy (mFOLFOX6 or CAPOX)

If OPRA with induction chemotherapy:

  • Up to 16 weeks of oxaliplatin-based chemotherapy (mFOLFOX6 or CAPOX), followed by
  • CRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine)

If OPRA with consolidation chemotherapy:

  • CRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine) followed by
  • Up to 16 weeks of oxaliplatin-based chemotherapy (mFOLFOX6 or CAPOX)
Experimental: Conventional arm
  • SCRT (5 fractions of 5 Gy)
  • Surgery (according to the principle of TME) or watch & wait
  • Optional adjuvant chemotherapy

OR

  • LCCRT (25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine) followed by
  • Surgery (according to the principles of TME) or watch & wait, followed by
  • Optional adjuvant chemotherapy
Radiation: Short course radiotherapy
Patients will receive 5 daily fractions of radiotherapy. Each fraction will consist of 5 Gy for a total dose of 25 Gy.
Drug: Adjuvant chemotherapy (optional)
The choice of the adjuvant chemotherapy is to the investigator's discretion.
Procedure: Total mesorectal excision
Surgery must be performed according to the principles of total mesorectal excision. A "watch & wait" approach is allowed for those subjects who have clinical complete response according to the local assessment.
Radiation: Long course chemoradiotherapy
Patients will receive 25-28 fractions of 1.8-2.0 Gy each +/- a boost to the primary tumour and involved lymph nodes, for a total of 50-56 Gy of radiation combined with either continuous infusion fluorouracil or capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: At 3 years after randomisation
Overall survival (OS) will be calculated from randomisation to death from any cause.
At 3 years after randomisation
Progression-free survival
Time Frame: At 3 years after randomisation
Progression-free survival (PFS) will be calculated from randomisation to any of the following events: unresectable tumour due to local tumour progression, R2 resection of the primary tumour, loco-regional recurrence after an R0/R1 resection, distant metastases, or death from any cause.
At 3 years after randomisation
Any grade peripheral sensory neuropathy
Time Frame: At 3 years after randomisation
Any grade peripheral sensory neuropathy as assessed by the investigator according to the NCI-CTCAE v5.0 will be analysed.
At 3 years after randomisation
Grade ≥3 toxicities during treatment
Time Frame: At 3 years after randomisation
Grade ≥3 toxicities during treatment (i.e., from the 1st day of treatment until the EOT visit) as assessed by the investigator according to the NCI-CTCAE v5.0 will be analysed.
At 3 years after randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jules Bordet Institute

Investigators

  • Study Chair: Francesco Sclafani, Jules Bordet Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2024

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2033

Study Registration Dates

First Submitted

September 18, 2023

First Submitted That Met QC Criteria

September 18, 2023

First Posted (Actual)

September 25, 2023

Study Record Updates

Last Update Posted (Actual)

December 5, 2025

Last Update Submitted That Met QC Criteria

November 28, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IJB-SHAPERS-ODN-013

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Older People

Clinical Trials on Short course radiotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe