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

NCT06052332 | Recruiting DMC

• 1 other identifier: IJB-SHAPERS-ODN-013
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

Locally Advanced Rectal Cancer; Older People

Keywords

rectal cancer

Outcome Measures

Primary Outcomes (4)

• Overall survival

  Overall survival (OS) will be calculated from randomisation to death from any cause.

  At 3 years after randomisation

• Progression-free survival

  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

  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

  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

Study Arms (2)

Conventional arm

EXPERIMENTAL

* 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; Drug: Adjuvant chemotherapy (optional); Procedure: Total mesorectal excision; Radiation: Long course chemoradiotherapy

TNT arm

ACTIVE COMPARATOR

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; Combination Product: Total neoadjuvant therapy

Interventions

Short course radiotherapy RADIATION

Patients will receive 5 daily fractions of radiotherapy. Each fraction will consist of 5 Gy for a total dose of 25 Gy.

Conventional arm

Adjuvant chemotherapy (optional) DRUG

The choice of the adjuvant chemotherapy is to the investigator's discretion.

Conventional arm

Total mesorectal excision PROCEDURE

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.

Conventional arm; TNT arm

Total neoadjuvant therapy COMBINATION_PRODUCT

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)

TNT arm

Long course chemoradiotherapy RADIATION

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

Conventional arm

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥ 70 years old
• ECOG performance status (PS):
• ≤1 if age \> 75 years old
• ≤2 if age ≤ 75 years old
• Histologically or cytologically confirmed adenocarcinoma of the rectum
• Distal border of the tumour below the peritoneal reflection and within 15 cm of the anal verge
• 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.
• Adequate bone marrow function as defined below:
• Absolute neutrophil count ≥1,500/µL
• Haemoglobin ≥9 g/dL
• Platelets ≥100,000/µL
• 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

You may not qualify if:

• 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.
• Presence of metastatic disease or recurrent rectal tumour.
• Presence of grade ≥2 peripheral neuropathy according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0.
• 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.
• Any contraindication to pelvic irradiation as evaluated by the investigator.
• Known hypersensitivity reactions to the study drugs or to any excipients, premedications or non-investigational medicinal products or concomitant medications.
• 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).
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment.
• 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.
• Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
• Any previous treatment for rectal cancer.
• Use of brivudine, sorivudine or their chemically related analogues.

Sponsors & Collaborators

• Jules Bordet Institute: lead

Study Sites (19)

ZAS Antwerpen

Antwerp, Antwerpen, 2610, Belgium

RECRUITING

UZA Antwerpen

Edegem, Antwerpen, 2650, Belgium

RECRUITING

AZ Turnhout

Turnhout, Antwerpen, 2300, Belgium

RECRUITING

Institut Jules Bordet

Anderlecht, Brussels Capital, 1070, Belgium

RECRUITING

Chirec Delta

Auderghem, Brussels Capital, 1160, Belgium

RECRUITING

CHU Saint-Pierre

Brussels, Brussels Capital, 1000, Belgium

RECRUITING

CHU Brugmann

Brussels, Brussels Capital, 1020, Belgium

RECRUITING

UZ Gent

Ghent, East Flanders, 9000, Belgium

RECRUITING

AZ Nikolaas

Sint-Niklaas, East Flanders, 9100, Belgium

RECRUITING

Hôpital de Jolimont

Haine-Saint-Paul, Hainaut, 7100, Belgium

RECRUITING

Epicura

Hornu, Hainaut, 7301, Belgium

RECRUITING

CHU Ambroise Pare

Mons, Hainaut, 7000, Belgium

NOT YET RECRUITING

CHU de Liège - Sart Tilman

Liège, Liège, 4000, Belgium

RECRUITING

CHA Libramont

Libramont, Luxemburg, 6800, Belgium

RECRUITING

Grand Hôpital De Charleroi

Charleroi, Namur, 6000, Belgium

SUSPENDED

CHU Charleroi

Charleroi, Namur, 6042, Belgium

NOT YET RECRUITING

CHU UCL Namur

Godinne, Namur, 5530, Belgium

RECRUITING

CHR Sambre et Meuse (site Meuse)

Namur, Namur, 5000, Belgium

NOT YET RECRUITING

CHU St Elisabeth

Namur, Namur, 5000, Belgium

RECRUITING

Related Publications (1)

• Saude-Conde R, Vandamme T, De Backer M, Martinive P, Covas A, Deleporte A, Dermine A, Forget F, Geboes K, Gilliaux Q, Gokburun Y, Gonne E, Joye I, Lecomte S, Liberale G, Lybaert W, Moretti L, Mortier L, Mupingu Mwanawa S, Puleo F, Saad ED, Sinapi I, Annemans L, Buyse M, Sclafani F. Efficacy and safety of short-course radiotherapy versus total neoadjuvant therapy in older rectal cancer patients: a randomised pragmatic trial (SHAPERS). ESMO Gastrointest Oncol. 2024 Jun 5;4:100067. doi: 10.1016/j.esmogo.2024.100067. eCollection 2024 Jun.

  PMID: 41648032 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Francesco Sclafani

  Jules Bordet Institute

  STUDY CHAIR

Central Study Contacts

Sophie Lepannetier, phD

CONTACT

+32 (0)2 541 34 56; ctsu.shapers@hubruxelles.be

Ikram El Idrissi

CONTACT

+32 (0)2 541 30 81; ctsu.shapers@hubruxelles.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: September 25, 2023
• Study Start: February 7, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2033
• Last Updated: December 5, 2025

Record last verified: 2025-11

Locations

BE (19)