Rectal Cancer, Rectal Neoplasms Malignant, Rectum Carcinoma
Conditions
Keywords
rectal cancer, neoadjuvant chemotherapy, neoadjuvant radiotherapy
Brief summary
The purpose of this study is to determine whether 3 months of neoadjuvant CapOx is non-inferior to neoadjuvant radiotherapy in patients with moderate risk CRM- mid rectal cancer.
Detailed description
This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to 5x5 Gy neoadjuvant radiotherapy in moderate risk CRM-negative rectal cancer patients. This is a prospective multicenter open-label non-inferiority randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 4 cycles of neoadjuvant CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, surgery and 4 cycles of adjuvant CapOx chemotherapy or 5x5 Gy radiotherapy, surgery and 8 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on сN stage and clinical center. Patients with сT3c-T3dN0-1M0, cT1-T3dN2M0 cancer in the middle rectum are included. Chemoradiotherapy (50 Gy with concomitant capecitabine 825 mg/m2 per os bid on radiation days) will be performed for patients with tumor progression after neoadjuvant chemotherapy. The main hypothesis is that the 2-year local recurrence rate is non-inferior after neoadjuvant chemotherapy and neoadjuvant radiotherapy in moderate risk mid rectal cancer patients. The target accrual is 158 patients in each treatment arm (including 10% potential data loss) based on non-recurrence rate of 98% in investigated and 96% in the control group with a non-inferiority margin of 3%, α=0,05, power 80%. An interim analysis is planned after 50% of the patients will reach a 2-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI is subject to central review. Conduction of this study and data collection are controlled by a local institutional board.
Interventions
DRUGOxaliplatin
130 mg/m2 iv day 1, 4 cycles
DRUGCapecitabine
2000 mg/m2, bid, per os, days 1-14, 4 cycles
RADIATIONRadiotherapy
Pelvic radiotherapy dose: 44 Gy on regional nodes, 50 Gy on primary tumor
PROCEDURERectal cancer surgery
Laparoscopic or open total mesorectal excision
Sponsors
Blokhin's Russian Cancer Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent * Histologically verified colon rectal adenocarcinoma * сT3c-T3dN0-1M0, cT1-T3dN2M0. cancer of the middle rectum (based on pelvic MRI) * Tumor more than 2 mm from mesorectal fascia (based on pelvic MRI) * Eastern Cooperative Oncology Group (ECOG) status 0-2 * Haemoglobin (HGB) \> 90 g/L * Platelet Count (PLT) \> 120x10\*9/L * Serum creatinine \< 150 µmol/L * Total bilirubin \< 25 µmol/L
Exclusion criteria
* inability to obtain informed consent * distant metastases * synchronous or metachronous tumors * previous chemotherapy or radiotherapy * clinically significant cardiovascular disorders (myocardial infarction \< 6 months before visit, stroke \< \< 6 months before visit, instable angina \< 3 months before visit, arrhythmia, uncontrolled hypertension \> 160/100 mm hg * clinically significant neurological disorders * previous neuropathy 2 or higher * current infection or heavy systemic disease * pregnancy, breastfeeding * ulcerative colitis * individual intolerance to treatment components * proven dihydropyrimidine dehydrogenase (DPD) deficiency * participation in other clinical trials * psychiatric disorders, which render patient unable to follow instructions or understand his/her condition * technical inability to perform pelvic MRI * inability of long-term followup of the patient * HIV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 2-year local recurrence rate | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute chemotherapy toxicity | 6 months | Toxicity measured according to NCI-CTCAE v.5.0 |
| pathologic complete response rate (pCR) | 1 month | — |
| 2-year overall survival | 2 years | — |
| Adjuvant chemotherapy compliance | 6 months | Proportion of patients who receive a complete course of adjuvant chemotherapy |
| Operative morbidity | 30 days | Morbidity measured according to Clavien-Dindo classification |
| Neoadjuvant chemotherapy disease progression rate | 3 months | Proportion of patients with disease progression during neoadjuvant chemotherapy |
| Preoperative tumor-associated complications rate | 3 months | The rate of tumor-associated complications (bowel obastruction, bleeding etc) during neoadjuvant chemotherapy |
| 2-year disease-free survival | 2 years | — |
Countries
Russia
Outcome results
None listed