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

Locally Advanced Rectal Cancer Clinical Trial

— SHAPERS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06052332
• Other study ID #: IJB-SHAPERS-ODN-013
• Status: Recruiting
• Phase: N/A
• Start date: February 7, 2024
• Est. completion date: December 2033

Study information

• Verified date: March 2024
• Source: Jules Bordet Institute
• Contact: Tabatha Delsaute
• Phone: +32 (0)2 541 36 62
• Email: ctsu.shapers[@]hubruxelles.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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".

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: December 2033
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Older People
• Rectal Neoplasms

Intervention

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 ?uorouracil 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 ?uorouracil or capecitabine) followed by Up to 16 weeks of oxaliplatin-based chemotherapy (mFOLFOX6 or CAPOX)

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht	Brussels
Belgium	GZA Antwerpen	Antwerpen
Belgium	Chirec Delta	Auderghem	Brussels
Belgium	CHU Brugmann	Brussels
Belgium	CHU Saint-Pierre	Bruxelles
Belgium	Grand Hôpital De Charleroi	Charleroi	Namur
Belgium	UZA Antwerpen	Edegem	Antwerpen
Belgium	UZ Gent	Gent	East Flanders
Belgium	CHU UCL Namur	Godinne	Namur
Belgium	Hôpital de Jolimont	Haine-Saint-Paul	Hainaut
Belgium	Epicura	Hornu	Hainaut
Belgium	CHU de Liège - Sart Tilman	Liège
Belgium	CHR Sambre et Meuse (site Meuse)	Namur
Belgium	AZ Niklaas	Sint-Niklaas	East Flanders

Sponsors (1)

Lead Sponsor	Collaborator
Jules Bordet Institute

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival (OS) will be calculated from randomisation to death from any cause.	At 3 years after randomisation
Primary	Progression-free survival	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.	At 3 years after randomisation
Primary	Any grade peripheral sensory neuropathy	Any grade peripheral sensory neuropathy as assessed by the investigator according to the NCI-CTCAE v5.0 will be analysed.	At 3 years after randomisation
Primary	Grade =3 toxicities during treatment	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.	At 3 years after randomisation