NCT06052332

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

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 230 (estimated)
• Sponsor: Jules Bordet Institute · Academic / Other
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

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.

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".

Conditions

• Locally Advanced Rectal Cancer
• Older People

Interventions

Type	Name	Description
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.
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)
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

Timeline

• Start date: 2024-02-07
• Primary completion: 2029-12-01
• Completion: 2033-12-01
• First posted: 2023-09-25
• Last updated: 2025-12-05

Locations

19 sites across 1 country: Belgium