Efficacy and Safety of SCRT Versus TNT in Older Patients With Locally Advanced Rectal Cancer (SHAPERS)
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| ClinicalTrials.gov Identifier: NCT06052332 |
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Recruitment Status :
Recruiting
First Posted : September 25, 2023
Last Update Posted : April 9, 2024
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Sponsor:
Jules Bordet Institute
Information provided by (Responsible Party):
Jules Bordet Institute
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Locally Advanced Rectal Cancer Older People | Radiation: Short course radiotherapy Drug: Adjuvant chemotherapy (optional) Procedure: Total mesorectal excision Combination Product: Total neoadjuvant therapy | Not Applicable |
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".
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 230 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Health Services Research |
| Official Title: | Efficacy and Safety of Short-course Radiotherapy (SCRT) Versus Total Neoadjuvant Therapy in Older Patients With Locally Advanced Rectal Cancer: a Multicentre, Open-label, Randomised Pragmatic Clinical Trial |
| Actual Study Start Date : | February 7, 2024 |
| Estimated Primary Completion Date : | December 2029 |
| Estimated Study Completion Date : | December 2033 |
| Arm | Intervention/treatment |
|---|---|
Experimental: SCRT arm
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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. |
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Active Comparator: TNT arm
Rapido regimen:
Or Rapido light regimen:
Or OPRA with induction chemotherapy (INCT-CRT) regimen:
Or OPRA with consolidation chemotherapy (CRT-CNCT) regimen:
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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:
If RAPIDO light:
If OPRA with induction chemotherapy:
If OPRA with consolidation chemotherapy:
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Primary Outcome Measures :
- Overall survival [ Time Frame: At 3 years after randomisation ]Overall survival (OS) will be calculated from randomisation to death from any cause.
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 70 Years and older (Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age ≥ 70 years old
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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.
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Adequate bone marrow function as defined below:
- Absolute neutrophil count ≥1,500/µL
- Haemoglobin ≥9 g/dL
- Platelets ≥100,000/µL
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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.
Exclusion Criteria:
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06052332
Contacts
| Contact: Tabatha Delsaute | +32 (0)2 541 36 62 | ctsu.shapers@hubruxelles.be | |
| Contact: Laurène Huberty | +32 (0)2 541 73 76 | ctsu.shapers@hubruxelles.be |
Locations
| Belgium | |
| UZA Antwerpen | Recruiting |
| Edegem, Antwerpen, Belgium, 2650 | |
| Contact: Timon Vandamme, MD oncotrials@uza.be | |
| Principal Investigator: Timon Vandamme, MD | |
| Institut Jules Bordet | Recruiting |
| Anderlecht, Brussels, Belgium, 1070 | |
| Contact: Rita Institut Jules Bordet, MD rita.saudeconde@hubruxelles.be | |
| Principal Investigator: Rita Saude Conde, MD | |
| Chirec Delta | Not yet recruiting |
| Auderghem, Brussels, Belgium, 1160 | |
| Contact: Francesco Puleo, MD francesco_puleo@hotmail.com | |
| Principal Investigator: Francesco Puleo, MD | |
| UZ Gent | Not yet recruiting |
| Gent, East Flanders, Belgium, 9000 | |
| Contact: Karen Geboes, MD karen.geboes@uzgent.be | |
| Principal Investigator: Karen Geboes, MD | |
| AZ Niklaas | Not yet recruiting |
| Sint-Niklaas, East Flanders, Belgium, 9100 | |
| Contact: Willem Lybaert, MD willem.lybaert@telenet.be | |
| Principal Investigator: Willem Lybaert, MD | |
| Hôpital de Jolimont | Recruiting |
| Haine-Saint-Paul, Hainaut, Belgium, 7100 | |
| Contact: Alexandre Dermine, MD Alexandre.DERMINE@jolimont.be | |
| Principal Investigator: Alexandre Dermine, MD | |
| Epicura | Recruiting |
| Hornu, Hainaut, Belgium, 7301 | |
| Contact: Sandra Mupingu, MD sandra.mupingumwanawa@epicura.be | |
| Principal Investigator: Sandra Mupingu, MD | |
| Grand Hôpital De Charleroi | Recruiting |
| Charleroi, Namur, Belgium, 6000 | |
| Contact: Isabelle SINAPI, MD isabelle.sinapi@ghdc.be | |
| Principal Investigator: Isabelle SINAPI, MD | |
| CHU UCL Namur | Recruiting |
| Godinne, Namur, Belgium, 5530 | |
| Contact: Laurence FAUGERAS, MD laurence.faugeras@chuuclnamur.uclouvain.be | |
| Principal Investigator: Laurence FAUGERAS, MD | |
| GZA Antwerpen | Recruiting |
| Antwerpen, Belgium, 2610 | |
| Contact: Ines Joye, MD ines.joye@gza.be | |
| Principal Investigator: Ines Joye, MD | |
| CHU Brugmann | Recruiting |
| Brussels, Belgium, 1020 | |
| Contact: Sylvie Lecomte, MD sylvie.lecomte@chu-brugmann.be | |
| Principal Investigator: Sylvie Lecomte, MD | |
| CHU Saint-Pierre | Recruiting |
| Bruxelles, Belgium, 1000 | |
| Contact: Amelie Deleporte, MD amelie.deleporte@stpierre-bru.be | |
| Principal Investigator: Amelie Deleporte, MD | |
| CHR Sambre et Meuse (site Meuse) | Not yet recruiting |
| Namur, Belgium, 5000 | |
| Contact: Yeter Gokburun, MD yeter.gokburun@chrsm.be | |
| Principal Investigator: Yeter Gokburun, MD | |
Sponsors and Collaborators
Jules Bordet Institute
Investigators
| Study Chair: | Francesco Sclafani | Jules Bordet Institute |
| Responsible Party: | Jules Bordet Institute |
| ClinicalTrials.gov Identifier: | NCT06052332 |
| Other Study ID Numbers: |
IJB-SHAPERS-ODN-013 |
| First Posted: | September 25, 2023 Key Record Dates |
| Last Update Posted: | April 9, 2024 |
| Last Verified: | March 2024 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Jules Bordet Institute:
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rectal cancer |
Additional relevant MeSH terms:
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Rectal Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site |
Neoplasms Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Rectal Diseases |