None listed
Conditions
Brief summary
This study aims to assess the efficacy of Total Neoadjuvant Therapy in Early-Stage Low Rectal Cancer. Who is it for? You may be eligible for this study if you are a male or female, aged 18 to 85 years of age, with histologically confirmed rectal adenocarcinoma, lowest part of tumour within 10 cm of anal verge on MRI or sigmoidoscopy, cT2-T3, N0, M0 rectal cancer based on clinical staging, and no extramural vascular invasion (EMVI) or threatened Mesorectal fascia (MRF) on MRI. Study details Participants will undergo Total Neoadjuvant Therapy (TNT) for early-stage low rectal cancer, beginning with six weeks of long-course chemoradiotherapy, including modulated radiation therapy and 5-FU infusion or capecitabine chemotherapy. Patients then take a 2-4 week break before undergoing up to 16-18 weeks of consolidation chemotherapy. Patients begin receiving 4 cycles of mFOLFOX6/FOLFOX over 8 weeks or 3 cycles of CAPOX over 9 weeks. A first response assessment (comprising rectal exam, flexible sigmoidoscopy and MRI pelvis) determines further treatment adjustments (which may include early termination of chemotherapy or completion of the full course), followed by a second response assessment if necessary. To ensure real-world applicability, chemotherapy regimen variations are permitted within set constraints, requiring at least 4 cycles of FOLFOX (up to 8) or at least 3 cycles of CAPOX (up to 6). Additionally, dose modifications or early discontinuation due to toxicity or poor tolerance remain at the treating team’s discretion. This flexible approach aims to optimise treatment while accommodating individual patient needs. During and after the intervention, participants will be assessed utilising modalities such as rectal exam, flexible sigmoidoscopy and MRI pelvis. Subsequent surveillance will also include blood tests, CT scans and colonoscopies. It is hoped that this research will demonstrate a structured yet adaptable TNT approach to improve outcomes for patients with early-stage low rectal cancer, laying the foundation for a new standard care option in these patients.
Interventions
This trial is an investigator-initiated, multicentre, single-arm phase II study. In this study, patients with early-stage (cT2-3, N0, M0) low rectal cancer will receive Total Neoadjuvant Therapy (TNT).
The preferred regime for consolidation TNT comprises the following:
• Long course chemoradiotherapy (6 weeks)
o 50 Gy external beam modulated radiation in 25 fractions over 5 weeks
o 5-FU infusion via pump for the period, or capecitabine orally 5 days per week
• Wait 2-4 weeks after completion
This trial is an investigator-initiated, multicentre, single-arm phase II study. In this study, patients with early-stage (cT2-3, N0, M0) low rectal cancer will receive Total Neoadjuvant Therapy (TNT). The preferred regime for consolidation TNT comprises the following: • Long course chemoradiotherapy (6 weeks) o 50 Gy external beam modulated radiation in 25 fractions over 5 weeks o 5-FU infusion via pump for the period, or capecitabine orally 5 days per week • Wait 2-4 weeks after completion of radiotherapy • Consolidation chemotherapy (total 16-18 weeks) o 4 cycles mFOLFOX6/ FOLFOX, 2nd weekly for 8 weeks OR 3 cycles CAPOX for 9 weeks o Then complete first response assessment (comprises rectal exam, flexible sigmoidoscopy and MRI pelvis) o Depending on outcome of above, give remaining 4 cycles of mFOLFOX6 (or FOLFOX) OR 3 cycles of CAPOX • Wait 2-4 weeks and perform second response assessment (comprises rectal exam, flexible sigmoidoscopy and MRI pelvis) Chemotherapy agents • mFOLFOX6/FOLFOX o Oxaliplatin, 85 mg/m2 intravenous (IV) infusion on day 1 of cycle o Calcium Folinate (Leucovorin) 50 mg IV bolus on day 1 of cycle o Fluorouracil 400 mg/m2 IV and 2400 mg/m2 IV infusion via pump over 46 hours on day 1 of cycle • CAPOX o Oxaliplatin 130 mg/m2 IV infusion on day 1 of cycle o Capecitabine 1000 mg/m2 twice a day orally for 2 weeks Variations of neoadjuvant therapy and dose adaptations To maximise opportunity for enrolment and best reflect the heterogeneity of real-world clinical practice, variations in TNT protocols at the discretion of the treating team will be allowed for within the following constraints: • If FOLFOX is utilised, intended course must comprise no less than 4 cycles, up to 8 cycles • If CAPOX is utilised, intended course must comprise no less than 3 cycles, up to 6 cycles Dose adaptations (i.e. dose reduction in event of poor tolerance or toxicity) or early cessation of neoadjuvant therapy is left at the discretion of the treating team. Adherence will be assessed through attendance at outpatient oncology sessions and review of medical records.
This trial is an investigator-initiated, multicentre, single-arm phase II study. In this study, patients with early-stage (cT2-3, N0, M0) low rectal cancer will receive Total Neoadjuvant Therapy (TNT).
The preferred regime for consolidation TNT comprises the following:
• Long course chemoradiotherapy (6 weeks)
o 50-54 Gy external beam modulated radiation in 25-27 fractions over 5 weeks
o 5-FU infusion via pump for the period, or capecitabine orally 5 days per week
• Wait 2-4 weeks after comp
This trial is an investigator-initiated, multicentre, single-arm phase II study. In this study, patients with early-stage (cT2-3, N0, M0) low rectal cancer will receive Total Neoadjuvant Therapy (TNT). The preferred regime for consolidation TNT comprises the following: • Long course chemoradiotherapy (6 weeks) o 50-54 Gy external beam modulated radiation in 25-27 fractions over 5 weeks o 5-FU infusion via pump for the period, or capecitabine orally 5 days per week • Wait 2-4 weeks after completion of radiotherapy • Consolidation chemotherapy (total 16-18 weeks) o 4 cycles mFOLFOX6/ FOLFOX, 2nd weekly for 8 weeks OR 3 cycles CAPOX for 9 weeks o Then complete first response assessment (comprises rectal exam, flexible sigmoidoscopy and MRI pelvis) o Depending on outcome of above, give remaining 4 cycles of mFOLFOX6 (or FOLFOX) OR 3 cycles of CAPOX • Wait 2-4 weeks and perform second response assessment (comprises rectal exam, flexible sigmoidoscopy and MRI pelvis) Chemotherapy agents • mFOLFOX6/FOLFOX o Oxaliplatin, 85 mg/m2 intravenous (IV) infusion on day 1 of cycle o Calcium Folinate (Leucovorin) 50 mg IV bolus on day 1 of cycle o Fluorouracil 400 mg/m2 IV and 2400 mg/m2 IV infusion via pump over 46 hours on day 1 of cycle • CAPOX o Oxaliplatin 130 mg/m2 IV infusion on day 1 of cycle o Capecitabine 1000 mg/m2 twice a day orally for 2 weeks Variations of neoadjuvant therapy and dose adaptations To maximise opportunity for enrolment and best reflect the heterogeneity of real-world clinical practice, variations in TNT protocols at the discretion of the treating team will be allowed for within the following constraints: • If FOLFOX is utilised, intended course must comprise no less than 4 cycles, up to 8 cycles • If CAPOX is utilised, intended course must comprise no less than 3 cycles, up to 6 cycles Dose adaptations (i.e. dose reduction in event of poor tolerance or toxicity) or early cessation of neoadjuvant therapy is left at the discretion of the treating team. Adherence will be assessed through attendance at outpatient oncology sessions and review of medical records.
Sponsors
Royal Adelaide Hospital / Central Adelaide Local Health Network
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria (patients must meet all the following criteria): • Age 18-85 years. • Histologically confirmed rectal adenocarcinoma. • Lowest part of tumour within 10 cm of anal verge on MRI or sigmoidoscopy. • cT2-T3, N0, M0 rectal cancer based on clinical staging. • No extramural vascular invasion (EMVI) or threatened Mesorectal fascia (MRF) on MRI.
Exclusion criteria
• Unable to undergo MRI staging • Malignant polyp / T1 cancer • Deficient mismatch repair (dMMR) / microsatellite instability high (MSI-H) cancer • Recurrent rectal cancer • Prior pelvic radiotherapy • Prior chemotherapy or surgery for rectal cancer (including diverting colostomy or transanal excision) prior to the initiation of neoadjuvant therapy • Women who are pregnant / within 28 days post-partum / breast feeding / wishing to preserve ovarian function / fertility • Active infections requiring systemic antibiotic treatment • Other active malignancy (with exception of adequately treated basal cell / squamous cell skin cancer or in situ cervical cancer) • Inability to provide informed consent
Outcome results
None listed