Comparing two treatment options for older patients with advanced rectal cancer

Efficacy and Safety of Conventional Neoadjuvant Therapy Versus Total Neoadjuvant Therapy in Older Patients With Locally Advanced Rectal Cancer: a Multicentre, Open-label, Randomised Pragmatic Clinical Trial

This study is testing whether short course radiotherapy or total neoadjuvant therapy works better for older patients with advanced rectal cancer.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 230 (estimated)
• Ages: 70 Years and up
• Sex: All
• Sponsor: Jules Bordet Institute (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 19 sites (Antwerp, Antwerpen and 18 other locations)
• Trial ID: NCT06052332 on ClinicalTrials.gov

What this trial studies

The SHAPERS study is a multicentre, open-label, randomised clinical trial designed to compare the efficacy and safety of short course radiotherapy (SCRT) versus total neoadjuvant therapy (TNT) in older patients aged 70 and above with high-risk stage II and stage III rectal cancer. Participants will be randomly assigned to one of the two treatment arms, with SCRT followed by surgery or watch & wait, or various regimens of TNT followed by surgery or watch & wait. The study aims to determine which treatment approach provides better outcomes for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are older adults aged 70 years and above with operable high-risk stage II or stage III rectal cancer.

Not a fit: Patients with early-stage rectal cancer or those who are not operable may not receive benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for older patients with locally advanced rectal cancer, potentially enhancing their survival and quality of life.

How similar studies have performed: Other studies have shown promising results with similar treatment approaches, indicating potential for success in this trial.

Eligibility criteria

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.

Where this trial is running

Antwerp, Antwerpen and 18 other locations

• ZAS Antwerpen — Antwerp, Antwerpen, Belgium (RECRUITING)
• UZA Antwerpen — Edegem, Antwerpen, Belgium (RECRUITING)
• AZ Turnhout — Turnhout, Antwerpen, Belgium (RECRUITING)
• Institut Jules Bordet — Anderlecht, Brussels Capital, Belgium (RECRUITING)
• Chirec Delta — Auderghem, Brussels Capital, Belgium (RECRUITING)
• CHU Saint-Pierre — Brussels, Brussels Capital, Belgium (RECRUITING)
• CHU Brugmann — Brussels, Brussels Capital, Belgium (RECRUITING)
• UZ Gent — Ghent, East Flanders, Belgium (RECRUITING)
• AZ Nikolaas — Sint-Niklaas, East Flanders, Belgium (RECRUITING)
• Hôpital de Jolimont — Haine-Saint-Paul, Hainaut, Belgium (RECRUITING)
• Epicura — Hornu, Hainaut, Belgium (RECRUITING)
• CHU Ambroise Pare — Mons, Hainaut, Belgium (NOT_YET_RECRUITING)
• CHU de Liège - Sart Tilman — Liège, Liège, Belgium (RECRUITING)
• CHA Libramont — Libramont, Luxemburg, Belgium (RECRUITING)
• Grand Hôpital De Charleroi — Charleroi, Namur, Belgium (SUSPENDED)
• CHU Charleroi — Charleroi, Namur, Belgium (NOT_YET_RECRUITING)
• CHU UCL Namur — Godinne, Namur, Belgium (RECRUITING)
• CHR Sambre et Meuse (site Meuse) — Namur, Namur, Belgium (NOT_YET_RECRUITING)
• CHU St Elisabeth — Namur, Namur, Belgium (RECRUITING)

Study contacts

• Study coordinator: Sophie Lepannetier, phD

Conditions: Locally Advanced Rectal Cancer, Older People, rectal cancer