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SHAPERS: Efficacy and Safety of SCRT Versus TNT in Older Patients With Locally Advanced Rectal Cancer

Sponsor
Jules Bordet Institute (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06052332
Collaborator
(none)
230
Enrollment
13
Locations
2
Arms
120
Anticipated Duration (Months)
17.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
  • Radiation: Short course radiotherapy
  • Drug: Adjuvant chemotherapy (optional)
  • Procedure: Total mesorectal excision
  • Combination Product: Total neoadjuvant therapy
 N/A

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".

Study Design

Study Type:
Interventional
Anticipated 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
Anticipated Study Start Date :
Dec 1, 2023
Anticipated Primary Completion Date :
Dec 1, 2029
Anticipated Study Completion Date :
Dec 1, 2033

Arms and Interventions

Arm Intervention/Treatment
Experimental: SCRT arm

SCRT (5 fractions of 5 Gy) Surgery (according to the principle of TME) or watch & wait 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.
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)

Outcome Measures

Primary Outcome Measures

  1. Overall survival [At 3 years after randomisation]

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

  2. 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.

  3. 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.

  4. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
70 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Age ≥ 70 years old

  2. ECOG performance status (PS):

  • ≤1 if age > 75 years old

  • ≤2 if age ≤ 75 years old

  1. Histologically or cytologically confirmed adenocarcinoma of the rectum

  2. Distal border of the tumour below the peritoneal reflection and within 15 cm of the anal verge

  3. 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.

  4. Adequate bone marrow function as defined below:

  • Absolute neutrophil count ≥1,500/µL

  • Haemoglobin ≥9 g/dL

  • Platelets ≥100,000/µL

  1. 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

  1. Adequate renal function as defined by estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73m² (according to the CKD-EPI 2021 equation).

  2. Absence of clinical conditions that in the opinion of the investigator, would contraindicate neoadjuvant therapy and/or surgery.

  3. Signed Informed Consent form (ICF) obtained prior to any study related procedure.

  4. 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 ≥1 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. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency.

  11. Any previous treatment for rectal cancer.

Contacts and Locations

Locations

Site City State Country Postal Code
1 UZA Antwerpen Edegem Antwerpen Belgium 2650
2 Institut Jules Bordet Anderlecht Brussels Belgium 1070
3 Chirec Delta Auderghem Brussels Belgium 1160
4 UZ Gent Gent East Flanders Belgium 9000
5 AZ Niklaas Sint-Niklaas East Flanders Belgium 9100
6 Hôpital de Jolimont Haine-Saint-Paul Hainaut Belgium 7100
7 Epicura Hornu Hainaut Belgium 7301
8 Grand Hôpital De Charleroi Charleroi Namur Belgium 6000
9 CHU UCL Namur Godinne Namur Belgium 5530
10 GZA Antwerpen Antwerpen Belgium 2610
11 CHU Brugmann Brussels Belgium 1020
12 CHU Saint-Pierre Bruxelles Belgium 1000
13 CHR Sambre et Meuse (site Meuse) Namur Belgium 5000

Sponsors and Collaborators

  • Jules Bordet Institute

Investigators

  • Study Chair: Francesco Sclafani, Jules Bordet Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT06052332
Other Study ID Numbers:
  • IJB-SHAPERS-ODN-013
First Posted:
Sep 25, 2023
Last Update Posted:
Sep 25, 2023
Last Verified:
Aug 1, 2023
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Jules Bordet Institute
rectal cancer
Additional relevant MeSH terms:
Rectal Neoplasms

Study Results

No Results Posted as of Sep 25, 2023