To hear about similar clinical trials, please enter your email below

Trial Title: Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy for Rectal Cancer: A Randomized Controlled Trial

NCT ID: NCT05496491

Condition: Rectal Neoplasms

Conditions: Official terms:
Rectal Neoplasms

Conditions: Keywords:
rectal
cancer
neoadjuvant
radiotherapy
chemotherapy
mesorectal
excision

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: The study will employ a prospective, parallel randomized-controlled design

Primary purpose: Treatment

Masking: None (Open Label)

Masking description: There will be no blindness at the level of the patient, the treating physicians (surgeon, oncologist, radiotherapist) and the researcher who will record the data.

Intervention:

Intervention type: Radiation
Intervention name: Neoadjuvant Chemoradiotherapy
Description: 5-week neoadjuvant radiotherapy regimen (28 x 1.8 Gy) combined with Capecitabine (bid 800 mg/m2, twice daily, on days 1-33-38)
Arm group label: Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy
Arm group label: Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy

Other name: nCRT

Intervention type: Drug
Intervention name: Adjuvant Chemotherapy
Description: 8 cycles of CAPOX (Capecitabine bid 1000 mg/m2, twice daily, day 1-14, every 3 weeks and Oxaliplatin 130 mg/m2, day 1, every 3 weeks) or alternatively, 12 cycles of folinate, fluorouracil and oxaliplatin (FOLFOX)
Arm group label: Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy

Other name: AC

Intervention type: Drug
Intervention name: Consolidation Chemotherapy
Description: CAPOX (Capecitabine bid1000 mg/m2 and Oxaliplatin 130 mg/m2, day 1, every 3 weeks) or alternatively FOLFOX
Arm group label: Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy

Other name: CC

Summary: The purpose of this protocol is to compare neoadjuvant chemoradiation plus consolidation chemotherapy before surgical resection with the standard neoadjuvant chemoradiation followed by surgical resection and adjuvant chemotherapy in patients with rectal cancer.

Detailed description: Colorectal cancer is the second leading cause of cancer-related deaths worldwide. It is estimated that 10% of cancer mortality is attributed to malignant neoplasms of the colon and rectum. More specifically, in the United States alone, 53,200 colorectal cancer deaths were reported. The current treatment of choice for locally advanced rectal cancer (Stage II/ III) is the combination of neoadjuvant chemoradiation followed by radical surgical resection based on the principles of total mesorectal excision (TME) after a 8-12 weeks period. Therapy is usually completed with the administration of adjuvant chemotherapy based on oxaliplatin and fluoropyrimidines. This combined approach allowed the reduction of local recurrence at levels around 5%. Despite the impressive results in local control, the same was not confirmed for the long-term, overall survival. Possible explanations to that are: a) the compliance and completion of the treatment schemes during the postoperative period were low and b) there was a delay in the administration of adjuvant chemotherapy; both could lead to subclinical metastatic disease progression. On the basis of achieving both goals, (i.e., local control through neoadjuvant radiotherapy and metastatic disease control through systemic chemotherapy) the administration of the two therapies in the preoperative period was proposed, in the form of combined or total neoadjuvant therapy. Additional theoretical benefits of total neoadjuvant therapy is faster defunctioning stoma reversal, as well as, the possibility of a more accurate evaluation of the tumor biological behavior, thus enabling a safer staging for patients who would be candidates for a watch and wait protocol. Furthermore, for patients who will eventually undergo surgery, total neoadjuvant therapy could probably increase R0 resection and sphincter-preservation rates. However, many researchers question the safety and efficacy of total neoadjuvant therapy. First, the administration of neoadjuvant chemotherapy significantly increases the risk of severe toxicity from cytotoxic agents. At the same time, according to the results of one of the largest prospective randomized trials, the addition of neoadjuvant chemotherapy into the treatment algorithm did not offer any advantage in the pathological response, 5-year overall and disease-free survival rates. Finally, there is considerable heterogeneity in the current literature, most likely reflecting the different schemes used in different trials regarding the radiotherapy regimen, the chemotherapy regimen as well as the sequence of each one in each protocol. The investigators believe that it is difficult to interpret any differences in results when multiple parameters have been changed in a comparative trial. For this reason when testing the current standard neoadjuvant protocol to the new trend of total neoadjuvant therapy it was decided to keep the same scheme and timing for the experimental group while the only parameter which was different was the use of the classic chemotherapy scheme during the waiting period following chemoradiation and before surgery.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Histologically confirmed rectal adenocarcinoma - cT3, cT4, threatened CRM / MRF, EMVI (+), ≥N1 - Multidisciplinary tumor board decision for neoadjuvant treatment - Tumor distance from the anal verge <15 cm based on endoscopy or magnetic resonance imaging - Patient 18 to 80 years old - General health condition status WHO 0-1 - Absence of co-morbidities that may affect treatment - Neutrophils >1,500 / mm3, platelets >100,000 / mm3, hemoglobin> 10 g / dL, normal creatinine, and creatinine clearance> 50 mL / min - Signed informed consent of the patient Exclusion Criteria: - Distant metastases - Non-resectable cancer - Contraindications for the administration of chemotherapy - Previous pelvic radiotherapy or chemotherapy - History of inflammatory bowel disorders - History of angina, acute myocardial infarction or heart failure - Active sepsis or systemic infection - Untreated physical and mental disability - Synchronous malignancy - Pregnancy or breast-feeding - Lack of compliance with the protocol process - Non-granting of signed informed consent

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Department of Surgery, University Hospital of Larissa

Address:
City: Larissa
Zip: 41110
Country: Greece

Status: Recruiting

Contact:
Last name: Konstantinos Perivoliotis, MD

Phone: 00302413501000
Email: kperi19@gmail.com

Contact backup:
Last name: George Tzovaras, Professor

Phone: 00302413502804
Email: gtzovaras@hotmail.com

Investigator:
Last name: Konstantinos Perivoliotis, MD
Email: Principal Investigator

Investigator:
Last name: Ioannis Baloyiannis, Prof
Email: Sub-Investigator

Investigator:
Last name: Ioannis Samaras, MD
Email: Sub-Investigator

Investigator:
Last name: Athanasios Kotsakis, Prof
Email: Sub-Investigator

Investigator:
Last name: Georgios Kyrgias, Prof
Email: Sub-Investigator

Start date: August 30, 2022

Completion date: August 30, 2026

Lead sponsor:
Agency: Larissa University Hospital
Agency class: Other

Source: Larissa University Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05496491

Login to your account

Did you forget your password?