Induction and Consolidation Chemotherapy in Patients With Locally Advanced CRM-positive Rectal Cancer

Rectal Cancer Clinical Trial

— RuCorT-03  

Official title:

Induction and Consolidation Chemotherapy in Locally Advanced Rectal Cancer Patients With Circumferential Resection Margin Involvement: a Multicenter Prospective Randomized Phase III Clinical Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04135313
• Other study ID #: RuCorT-03
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: October 20, 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 the addition of 2 cycles of induction CapOx chemotherapy and 2 cycles of consolidation CapOx chemotherapy to standard chemoradiation improves 3-year disease-free survival in patients with locally advanced CRM"+" mid and low rectal cancer.

Description:

This trial aims to investigate the efficacy of adding neoadjuvant induction and consolidation chemotherapy compared to standard chemoradiotherapy in locally advanced rectal cancer patients with circumferential resection margin involvement. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy OR chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), surgery (10-12 weeks following chemoradiotherapy) and 6 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on N stage, tumor location in the middle or low rectum and clinical center. Patients with middle or low rectal cancer without distant metastases, with involved circumferential resection margin (based on pretreatment MRI) will be included.

The target accrual is 270 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 12% 3-yr disease-free survival (60% vs 72%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-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: 540
• 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 0-10 cm above the anal verge

• No distant metastases

• Circumferential resection margin (CRM) involvement (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

• cT2N0M0 rectal cancer

• 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
• Oxaliplatin
130 mg/m2 iv day 1
• 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, 54 Gy on primary tumor in 2 Gy fractions

Procedure:
• Rectal cancer surgery
Laparoscopic or open total mesorectal excision or extralevator abdominoperineal resection

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	3-year disease-free survival		3 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	local recurrence rate		3 years
Secondary	3-year overall survival		3 years
Secondary	Operative morbidity	Morbidity measured according to Clavien-Dindo classification	30 days
Secondary	Preoperative tumor-associated complications rate	The rate of tumor-associated complications (bowel obstruction, bleeding etc) during neoadjuvant chemotherapy	6 months
Secondary	Sphincter preservation rate		1 month