Efficacy and Safety of SCRT Versus TNT in Older Patients With Locally Advanced Rectal Cancer
- Conditions
- Locally Advanced Rectal CancerOlder People
- Interventions
- Radiation: Short course radiotherapyDrug: Adjuvant chemotherapy (optional)Combination Product: Total neoadjuvant therapyProcedure: Total mesorectal excision
- Registration Number
- NCT06052332
- Lead Sponsor
- Jules Bordet Institute
- 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.
- 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 SCRT arm or the TNT arm (The study design is shown in figure 3.1 and 3.2).
SCRT arm:
The SCRT 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
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".
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 230
-
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
-
Adequate renal function as defined by estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73m² (according to the CKD-EPI 2021 equation).
-
Absence of clinical conditions that in the opinion of the investigator, would contraindicate neoadjuvant therapy and/or surgery.
-
Signed Informed Consent form (ICF) obtained prior to any study related procedure.
-
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.
- 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 ≥1 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.
- Known complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- Any previous treatment for rectal cancer.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SCRT arm Total mesorectal excision * SCRT (5 fractions of 5 Gy) * Surgery (according to the principle of TME) or watch \& wait * Optional adjuvant chemotherapy SCRT arm Short course radiotherapy * SCRT (5 fractions of 5 Gy) * Surgery (according to the principle of TME) or watch \& wait * Optional adjuvant chemotherapy SCRT arm Adjuvant chemotherapy (optional) * SCRT (5 fractions of 5 Gy) * Surgery (according to the principle of TME) or watch \& wait * Optional adjuvant chemotherapy TNT arm Total mesorectal excision 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" TNT arm Total neoadjuvant therapy 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"
- Primary Outcome Measures
Name Time Method Overall survival At 3 years after randomisation Overall survival (OS) will be calculated from randomisation to death from any cause.
Any grade peripheral sensory neuropathy 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.
Progression-free survival 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.
Grade ≥3 toxicities during treatment 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (19)
UZA Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
Institut Jules Bordet
🇧🇪Anderlecht, Brussels, Belgium
Chirec Delta
🇧🇪Auderghem, Brussels, Belgium
UZ Gent
🇧🇪Gent, East Flanders, Belgium
AZ Turnhout
🇧🇪Turnhout, Antwerpen, Belgium
AZ Nikolaas
🇧🇪Sint-Niklaas, East Flanders, Belgium
Hôpital de Jolimont
🇧🇪Haine-Saint-Paul, Hainaut, Belgium
Epicura
🇧🇪Hornu, Hainaut, Belgium
CHU Ambroise Pare
🇧🇪Mons, Hainaut, Belgium
CHA Libramont
🇧🇪Libramont, Luxemburg, Belgium
Grand Hôpital De Charleroi
🇧🇪Charleroi, Namur, Belgium
CHU Charleroi
🇧🇪Charleroi, Namur, Belgium
CHU UCL Namur
🇧🇪Godinne, Namur, Belgium
ZAS Antwerpen
🇧🇪Antwerpen, Belgium
CHU Brugmann
🇧🇪Brussels, Belgium
CHU Saint-Pierre
🇧🇪Bruxelles, Belgium
CHU de Liège - Sart Tilman
🇧🇪Liège, Belgium
CHR Sambre et Meuse (site Meuse)
🇧🇪Namur, Belgium
CHU St Elisabeth
🇧🇪Namur, Belgium