Neoadjuvant Chemotherapy in Patients With Moderate Risk Mid Rectal Cancer (RuCorT-02)

A Multicenter Prospective Phase III Clinical Trial of Neoadjuvant CapOx in Patients With Intermediate Risk CRM-negative Middle Rectal Cancer

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Rectal Cancer; Rectum Carcinoma; Rectal Neoplasms Malignant
• Intervention / Treatment: Drug: Capecitabine; Drug: Capecitabine; Drug: Oxaliplatin; Radiation: Radiotherapy; Procedure: Rectal cancer surgery; Radiation: Radiotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 316
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • N.N.Blokhin Russian Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant chemotherapy; Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery within 2 weeks. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).	Drug: Capecitabine; 825 mg/m2, bid, per os, only on days of radiation (Monday through Friday); Other Names: Xeloda; Drug: Capecitabine; 2000 mg/m2, bid, per os, days 1-14, 4 cycles; Other Names: Xeloda; Drug: Oxaliplatin; 130 mg/m2 iv day 1, 4 cycles; Radiation: Radiotherapy; Pelvic radiotherapy dose: 44 Gy on regional nodes, 50 Gy on primary tumor; Procedure: Rectal cancer surgery; Laparoscopic or open total mesorectal excision; Radiation: Radiotherapy; Pelvic radiotherapy dose: 25 Gy in 5 Gy fractions
Active Comparator: Neoadjuvant radiotherapy; Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).	Drug: Capecitabine; 825 mg/m2, bid, per os, only on days of radiation (Monday through Friday); Other Names: Xeloda; Drug: Capecitabine; 2000 mg/m2, bid, per os, days 1-14, 4 cycles; Other Names: Xeloda; Drug: Oxaliplatin; 130 mg/m2 iv day 1, 4 cycles; Radiation: Radiotherapy; Pelvic radiotherapy dose: 44 Gy on regional nodes, 50 Gy on primary tumor; Procedure: Rectal cancer surgery; Laparoscopic or open total mesorectal excision; Radiation: Radiotherapy; Pelvic radiotherapy dose: 25 Gy in 5 Gy fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year local recurrence rate	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year overall survival		2 years
Adjuvant chemotherapy compliance	Proportion of patients who receive a complete course of adjuvant chemotherapy	6 months
Acute chemotherapy toxicity	Toxicity measured according to NCI-CTCAE v.5.0	6 months
pathologic complete response rate (pCR)		1 month
Operative morbidity	Morbidity measured according to Clavien-Dindo classification	30 days
2-year disease-free survival		2 years
Neoadjuvant chemotherapy disease progression rate	Proportion of patients with disease progression during neoadjuvant chemotherapy	3 months
Preoperative tumor-associated complications rate	The rate of tumor-associated complications (bowel obastruction, bleeding etc) during neoadjuvant chemotherapy	3 months

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center
• Investigators: Principal Investigator: Zaman Z Mamedli, PhD, N.N.Blokhin Russian Cancer Research Center

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2019
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: October 19, 2019
• First Submitted That Met QC Criteria: October 19, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 7, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: rectal cancer; neoadjuvant chemotherapy; neoadjuvant radiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: RuCorT-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No