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

NCT ID: NCT06052332

Last Updated: 2025-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-07

Study Completion Date

2033-12-31

Brief Summary

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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

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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

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Locally Advanced Rectal Cancer Older People

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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Conventional arm

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

Group Type EXPERIMENTAL

Short course radiotherapy

Intervention Type RADIATION

Patients will receive 5 daily fractions of radiotherapy. Each fraction will consist of 5 Gy for a total dose of 25 Gy.

Adjuvant chemotherapy (optional)

Intervention Type DRUG

The choice of the adjuvant chemotherapy is to the investigator's discretion.

Total mesorectal excision

Intervention Type PROCEDURE

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.

Long course chemoradiotherapy

Intervention Type RADIATION

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

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"

Group Type ACTIVE_COMPARATOR

Total mesorectal excision

Intervention Type PROCEDURE

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.

Total neoadjuvant therapy

Intervention Type COMBINATION_PRODUCT

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)

Interventions

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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.

Intervention Type RADIATION

Adjuvant chemotherapy (optional)

The choice of the adjuvant chemotherapy is to the investigator's discretion.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

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)

Intervention Type COMBINATION_PRODUCT

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

Intervention Type RADIATION

Eligibility Criteria

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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 ≥2 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. Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
11. Any previous treatment for rectal cancer.
12. Use of brivudine, sorivudine or their chemically related analogues.
Minimum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jules Bordet Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Francesco Sclafani

Role: STUDY_CHAIR

Jules Bordet Institute

Locations

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ZAS Antwerpen

Antwerp, Antwerpen, Belgium

Site Status RECRUITING

UZA Antwerpen

Edegem, Antwerpen, Belgium

Site Status RECRUITING

AZ Turnhout

Turnhout, Antwerpen, Belgium

Site Status RECRUITING

Institut Jules Bordet

Anderlecht, Brussels Capital, Belgium

Site Status RECRUITING

Chirec Delta

Auderghem, Brussels Capital, Belgium

Site Status RECRUITING

CHU Saint-Pierre

Brussels, Brussels Capital, Belgium

Site Status RECRUITING

CHU Brugmann

Brussels, Brussels Capital, Belgium

Site Status RECRUITING

UZ Gent

Ghent, East Flanders, Belgium

Site Status RECRUITING

AZ Nikolaas

Sint-Niklaas, East Flanders, Belgium

Site Status RECRUITING

Hôpital de Jolimont

Haine-Saint-Paul, Hainaut, Belgium

Site Status RECRUITING

Epicura

Hornu, Hainaut, Belgium

Site Status RECRUITING

CHU Ambroise Pare

Mons, Hainaut, Belgium

Site Status NOT_YET_RECRUITING

CHU de Liège - Sart Tilman

Liège, Liège, Belgium

Site Status RECRUITING

CHA Libramont

Libramont, Luxemburg, Belgium

Site Status RECRUITING

Grand Hôpital De Charleroi

Charleroi, Namur, Belgium

Site Status SUSPENDED

CHU Charleroi

Charleroi, Namur, Belgium

Site Status NOT_YET_RECRUITING

CHU UCL Namur

Godinne, Namur, Belgium

Site Status RECRUITING

CHR Sambre et Meuse (site Meuse)

Namur, Namur, Belgium

Site Status NOT_YET_RECRUITING

CHU St Elisabeth

Namur, Namur, Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Sophie Lepannetier, phD

Role: CONTACT

+32 (0)2 541 34 56

Ikram El Idrissi

Role: CONTACT

+32 (0)2 541 30 81

Facility Contacts

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Ines Joye, MD

Role: primary

Timon Vandamme, MD

Role: primary

Leen Mortier, MD

Role: primary

Rita Institut Jules Bordet, MD

Role: primary

Francesco Puleo, MD

Role: primary

Amelie Deleporte, MD

Role: primary

Sylvie Lecomte, MD

Role: primary

Karen Geboes, MD

Role: primary

Willem Lybaert, MD

Role: primary

Alexandre Dermine, MD

Role: primary

Sandra Mupingu, MD

Role: primary

Marie Diaz, MD

Role: primary

Elodie Gonne, MD

Role: primary

Frederic Forget, MD

Role: primary

Angélique Covas, MD

Role: primary

Laurence FAUGERAS, MD

Role: primary

Yeter Gokburun, MD

Role: primary

Donatienne Taylor, MD

Role: primary

Other Identifiers

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IJB-SHAPERS-ODN-013

Identifier Type: -

Identifier Source: org_study_id

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