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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06052332
Recruitment Status : Recruiting
First Posted : September 25, 2023
Last Update Posted : April 9, 2024
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute

Tracking Information
First Submitted Date  ICMJE September 18, 2023
First Posted Date  ICMJE September 25, 2023
Last Update Posted Date April 9, 2024
Actual Study Start Date  ICMJE February 7, 2024
Estimated Primary Completion Date December 2029   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2023)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of SCRT Versus TNT in Older Patients With Locally Advanced Rectal Cancer
Official Title  ICMJE 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
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".
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE
  • Locally Advanced Rectal Cancer
  • Older People
Intervention  ICMJE
  • 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)
Study Arms  ICMJE
  • Experimental: SCRT arm
    • SCRT (5 fractions of 5 Gy)
    • Surgery (according to the principle of TME) or watch & wait
    • Optional adjuvant chemotherapy
    Interventions:
    • Radiation: Short course radiotherapy
    • Drug: Adjuvant chemotherapy (optional)
    • Procedure: Total mesorectal excision
  • 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"
    Interventions:
    • Procedure: Total mesorectal excision
    • Combination Product: Total neoadjuvant therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 18, 2023)		 230
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2033
Estimated Primary Completion Date December 2029   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 70 years old

  2. ECOG performance status (PS):

    • ≤1 if age > 75 years old
    • ≤2 if age ≤ 75 years old
  3. Histologically or cytologically confirmed adenocarcinoma of the rectum
  4. Distal border of the tumour below the peritoneal reflection and within 15 cm of the anal verge
  5. 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.

  6. Adequate bone marrow function as defined below:

    • Absolute neutrophil count ≥1,500/µL
    • Haemoglobin ≥9 g/dL
    • Platelets ≥100,000/µL

  7. 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
  8. Adequate renal function as defined by estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73m² (according to the CKD-EPI 2021 equation).
  9. Absence of clinical conditions that in the opinion of the investigator, would contraindicate neoadjuvant therapy and/or surgery.
  10. Signed Informed Consent form (ICF) obtained prior to any study related procedure.
  11. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 70 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06052332
Other Study ID Numbers  ICMJE IJB-SHAPERS-ODN-013
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Jules Bordet Institute
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Jules Bordet Institute
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Francesco Sclafani Jules Bordet Institute
PRS Account Jules Bordet Institute
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP