Planned Non-operative Management for Rectal Cancer

Study Overview
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Brief Summary
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The investigators propose to conduct an observational study on consecutive patients with low-lying or mid rectal cancers smaller than 5 cm in length and less than 50% of rectal circumferential extent. The aim of this study is to test a hypothesis that escalation of either radiation or chemotherapy dose of the routine preoperative radio(chemo)therapy leads to an increase of clinical complete response rate. The planned sample size of 23 patients was calculated based on the assumption that clinical complete response rate after routine preoperative radio(chemo)therapy is 34% [1] and expected rate after radio(chemo)therapy dose escalation is 75% [2-4]. An endorectal high dose rate iridium brachytherapy boost (2 fractions of 10 Gy) will be added after the routine preoperative treatment consisted of external beam radiotherapy (5 × 5 Gy) combined with sequential 3 cycles of consolidation FOLFOX4. However, for patients with involvement of the anal canal, additional 3 cycles of consolidation FOLFOX4 (6 cycles in total) will be added instead of brachytherapy boost to avoid severe post-radiation toxicity.

Official Title
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Radio(Chemo)Therapy Dose Escalation in Non-operative Management for Rectal Cancer: A Prospective NOM-3 Observational Study

Conditions
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Rectal Cancer

Intervention / Treatment
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* Radiation: Radiotherapy boost
* Drug: Additional consolidation chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the rectum classified clinically as T2, T3a-c or T4b but only with superficial infiltration of the vagina or prostate; tumour accessible by digital rectal examination; tumour ≤5 cm in length and ≤50% of rectal circumferential extent; N0-N2, but mesorectal node <7 mm and no lateral nodes enlargement); extramural vascular invasion but not larger than 7 mm in the largest dimension; M0. Operable patient Patient having read the information note and having signed the informed consent Follow-up possible Exclusion Criteria: Inoperable patient cT1, cT3d, large T4, tumour ≥5cm or ≥50 of rectal circumferential extent Enlargement of lateral nodes or any node ≥8 mm in diameter Patient presenting metastasis at diagnosis Previous pelvic irradiation Simultaneous progressive another cancer Close follow-up uncertain.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: A dose escalation study, either radiotherapy dose escalation or chemotherapy dose escalation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: radiotherapy dose escalation<br>Additional two fractions of endorectal high dose rate iridium brachytherapy boost, 10 Gy each. | Radiation: Radiotherapy boost<br>* Additional endorectal high rate irydium brachytherapy boost, 2 fractions of 10 Gy each.<br>|
| Experimental: chemotherapy dose escalation<br>Additional three cycles of consolidation chemotherapy consisted of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4). | Drug: Additional consolidation chemotherapy<br>* Three additional cycles of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4) consolidation chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with clinical complete response. | Clinical complete response will be assessed by digital rectal examination, endoscopy and MRI. The analysis will take place 6 months after the start of treatment of a last enrolled patient. | 15 weeks from the radiation start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regrowth rate. | Regrowth rate will be accessed at 2 years in patients undergoing watch-and-wait. The analysis will take place 12 months after the start of treatment of a last enrolled patient. | From 12 months to 26 months from the radiation start. | 
| Anorectal function. | Anorectal function will be assessed by LARS scale before treatment and one year after the radiation start. | One year after the radiation start. | 
| Acute and late toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE), version 5. | Acute and late toxicity will be assessed by CTCAE v.5 scale. | From 12 months to 26 months from the radiation start. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, Non-operative management