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| Name | Class |
|---|---|
| Vilnius University | OTHER |
| Tomas Poskus, Faculty of Medicine, Vilnius University | UNKNOWN |
| Vilnius University Hospital Santaros Klinikos | OTHER |
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This study hypothesizes that approximately 50% of rectal cancer patients can preserve their rectum using a watch-and-wait strategy if they achieve a complete or near-complete clinical response to total neoadjuvant therapy (TNT). The objective is to determine whether the complications, quality of life, and survival rates of rectal cancer patients who have achieved a complete or near-complete clinical response to TNT, followed by a watch-and-wait approach, are comparable to those of patients who undergo surgery first. Additionally, the study aims to identify potential prognostic and predictive markers for rectal cancer and examine survival rates and factors influencing responses to chemoradiotherapy (CRT) or TNT.
The study is divided into two parts:
**Part One:** Participants with cT1N1, T2-T3 N0-1 rectal cancer, MRF-, and EMVI-, with surgery as one of the possible first-line treatment options, will be randomized into two groups. The experimental group will consist of participants receiving TNT, including CRT and consolidation chemotherapy (Ch). If these participants achieve a complete or near-complete clinical response, they will be observed using a watch-and-wait strategy, which is a non-operative approach. The control group will consist of participants who undergo surgical treatment initially.
**Part Two:** All participants with rectal cancer who have received CRT or TNT will be included. Additionally, participants diagnosed with rectal cancer who are scheduled for CRT or TNT but declined to participate in Part One or do not meet the inclusion criteria will also be included.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part one. The first group: an experimental group - TNT, organ preservation. | Experimental | Participants in the experimental group will be treated with TNT - CRT plus consolidating Ch. Consolidation Ch lasts 12 weeks. The response to TNT will be assessed 4 to 5 weeks after the last cycle of Ch. Response assessment will be performed through digital examination, pelvic MRI, rectoscopy, and biopsy. Participants will be actively followed up and not treated after a complete or near-complete response. In case of non-response, participants will undergo surgery. If the participant is diagnosed with a near-complete clinical response and wishes to avoid surgery, the response is reassessed after 8 weeks. If there is no response, i.e., near-complete clinical response persists, the participant is offered surgery. Participants in the experimental group do not receive adjuvant treatment after TNT and surgery. |
|
| Part one. Second Group: a control Group - surgery | Active Comparator | In the control group, treatment will start with surgery. Following surgical treatment, adjuvant therapy may be provided for control group participants according to standard clinical practice if indicated. | |
| Part two of the study | Other | In the second part of the study, investigators will prospectively collect and analyze the personal medical records of participants who have already received treatment with CRT or TNT. No new diagnostic or therapeutic approaches will be implemented; routine clinical practices for long-term follow-up will continue. For participants who have not received specific treatment and do not meet the inclusion criteria for the first part of the study, as well as those who declined to participate in that part, investigators will follow the routine clinical practices for investigation, treatment, and follow-up as long as they meet the inclusion criteria for the second part of the study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiation Therapy | Radiation | Radiation therapy (RT) is administered at a dose of 2 Gy per day for a total dose of 50 Gy delivered to the pelvis. This is done throughout 5 to 6 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative complications | Assessed based on the Clavien Dindo classification. | From the start of treatment until 3 months after surgery. |
| TNT toxicity | Local and systemic toxicity and (or) side effects will be recorded according to the general terminology criteria for adverse events version 5.0 (CTCAE v5.0). | From the start of treatment until 3 months after TNT. |
| Mortality rate | Mortality after TNT or surgery. | From the start of treatment until 3 months after treatment. |
| Quality of life | Quality of life Will be assessed using scoring manual of European Organisation For Research And Treatment Of Cancer of CR29 (Colorectal). | From the start of treatment until 3 years after treatment. |
| Low anterior resection syndrome rate. | Assessed based on the LARS questionnaire | From the start of treatment until 3 years after treatment. |
| Fatigue | Fatigue will be assessed using scoring manual of the functional assessment of chronic illness therapy - fatigue (FACIT-F) questionnaire. | From the start of treatment until 3 years after treatment |
| Complete clinical response rate | Criteria for Complete Clinical Response DRE:
Endoscopy:
MRT:
|
| Measure | Description | Time Frame |
|---|---|---|
| Rectal preservation rate | Percentage of participants achieving complete or near-complete clinical response and rectal preservation using a "watch and wait" approach. | 3 years after TNT |
| Local regrowth rate |
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Part One
Inclusion Criteria:
Exclusion Criteria:
Part Two
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ernestas Šileika, MD | Contact | +37060950402 | ernestas.sileika@nvc.santa.lt | |
| Audrius Dulskas, PhD | Contact | +370 675 20094 | audrius.dulskas@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Tomas Poškus, PhD | Translational Health Research Institute, Faculty of Medicine, Vilnius University Ciurlionio str. 21, LT-03101 Vilnius | Study Chair |
| Audrius Dulskas, PhD | General and Abdominal Surgery and Oncology Department, National Cancer Institute, Vilnius, Lithuania |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nacional Cancer Institute | Recruiting | Vilnius | 08660 | Lithuania |
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| Research Council of Lithuania |
| OTHER |
**Part One:** A prospective randomized study. Participants will be randomly divided into two groups: an experimental group and a control group.
**Part Two:** A prospective cohort study. In the second part of the study, there is no planned allocation of groups.
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| Chemoradiotherapy | Drug | Capecitabine: 825 mg/m² twice daily, prescribed 1-5 days per week, for 5 weeks during RT. Or Bolus 5-FU regimen: 5-fluorouracil (5-FU) 400 mg/m2/day intravenously, administered on days 1-4 and 33-35. Calcium folinate (folinic acid) 20 mg/m2/day intravenously on days 1-4 and 33-35. |
|
| Consolidation Chemotherapy | Drug | XELOX: Oxaliplatin 130 mg/m² (day 1) + capecitabine 1000 mg/m² (days 1-14), every 3 weeks for 4 cycles. Or FOLFOX: Oxaliplatin - 85 mg/m2 intravenously (2-hour infusion), drip for 1 day. Calcium folinate (folinic acid) - 400 mg/m2/d. intravenously (2-hour infusion), started on day 1. F(5-fluorouracil) - 400 mg/m2/d. intravenously (bolus), started on day 1. Repeat every 2 weeks for 6 times. |
|
| Surgery | Procedure | Transabdominal Resection: Abdominoperineal resection, low anterior resection, or coloanal anastomosis using total mesorectal excision. |
|
| Part two | Other | Standard treatment protocols and follow-up procedures are implemented in clinical practice. |
|
| Adjuvant treatment | Other | If indicated, adjuvant therapy will be administered as usual in clinical practice. |
| 12 - 14 weeks after TNT |
| Near-complete clinical response rate | Near Complete Response DRE: - Smooth induration or superficial minor mucosal irregularity Endoscopic:
| 12 - 14 weeks after TNT |
Percentage of participants with tumor regrowth after watch-and-wait when a complete or near-complete clinical response was achieved after TNT
| 3 years after TNT |
| Overall survival | The time between enrolment and death from any cause. | 3 - 5 years. |
| Disease-free survival | The time between enrolment and the first documented disease progression, i.e. local recurrence or metastasis, or death from any cause. | 3 - 5 years. |
| Local recurrence-free survival | Local recurrence rates in participants who underwent surgery. | 3 - 5 years. |
| Distant metastasis-free survival | Incidence of distant metastases | 3 - 5 years. |
| Stoma free survival | Stoma-free survival is defined as the period after treatment during which the patient does not develop a stoma. | 3 - 5 years. |
| Principal Investigator |
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| D011832 | Radiation Injuries |
| D000094123 | Low Anterior Resection Syndrome |
| D005221 | Fatigue |
| D011183 | Postoperative Complications |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D014947 | Wounds and Injuries |
| D003108 | Colonic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D059248 | Chemoradiotherapy |
| D060830 | Consolidation Chemotherapy |
| D013514 | Surgical Procedures, Operative |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D003131 | Combined Modality Therapy |
| D004358 | Drug Therapy |
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