Neoadjuvant Chemotherapy in Patients With Moderate Risk Mid Rectal Cancer

Rectal Cancer Clinical Trial

— RuCorT-02  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04134897
• Other study ID #: RuCorT-02
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: October 14, 2019
• Est. completion date: October 2024

Study information

• Verified date: February 2021
• Source: Blokhin's Russian Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 316
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Informed consent
• Histologically verified colon rectal adenocarcinoma
• ?T3c-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

Related Conditions & MeSH terms

• Neoplasms
• Rectal Cancer
• Rectal Neoplasms
• Rectal Neoplasms Malignant
• Rectum Carcinoma

Intervention

Drug:
• Capecitabine
2000 mg/m2, bid, per os, days 1-14, 4 cycles
• Oxaliplatin
130 mg/m2 iv day 1, 4 cycles
• Capecitabine
825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)

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

Locations

Country	Name	City	State
Russian Federation	N.N.Blokhin Russian Cancer Research Center	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Blokhin's Russian Cancer Research Center

Country where clinical trial is conducted

Russian Federation, 

Outcome

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