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