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Induction and Consolidation Chemotherapy in Patients With Locally Advanced CRM-positive Rectal Cancer (RuCorT-03)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04135313
Recruitment Status : Enrolling by invitation
First Posted : October 22, 2019
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Sergey Gordeyev, Blokhin's Russian Cancer Research Center

Brief 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.

Condition or disease Intervention/treatment Phase
Rectal Neoplasms Malignant Rectum Carcinoma Rectal Cancer Drug: Capecitabine Drug: Oxaliplatin Radiation: Radiotherapy Procedure: Rectal cancer surgery Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 540 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 20, 2019
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Arm Intervention/treatment
Experimental: Neoadjuvant chemotherapy
Patients receive 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
Drug: Capecitabine
2000 mg/m2, bid, per os, days 1-14
Other Name: Xeloda

Drug: Oxaliplatin
130 mg/m2 iv day 1

Drug: Capecitabine
825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
Other Name: Xeloda

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

Active Comparator: Chemoradiotherpy
Patients receive 54 Gy pelvic chemoradiotherapy in 2 Gy fractions with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 10-12 weeks. After surgery patients receive 6 cycles of adjuvant CapOx chemotherapy.
Drug: Capecitabine
2000 mg/m2, bid, per os, days 1-14
Other Name: Xeloda

Drug: Oxaliplatin
130 mg/m2 iv day 1

Drug: Capecitabine
825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
Other Name: Xeloda

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




Primary Outcome Measures :
  1. 3-year disease-free survival [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Adjuvant chemotherapy compliance [ Time Frame: 6 months ]
    Proportion of patients who receive a complete course of adjuvant chemotherapy

  2. Acute chemotherapy toxicity [ Time Frame: 6 months ]
    Toxicity measured according to NCI-CTCAE v.5.0

  3. pathologic complete response rate (pCR) [ Time Frame: 1 month ]
  4. local recurrence rate [ Time Frame: 3 years ]
  5. 3-year overall survival [ Time Frame: 3 years ]
  6. Operative morbidity [ Time Frame: 30 days ]
    Morbidity measured according to Clavien-Dindo classification

  7. Preoperative tumor-associated complications rate [ Time Frame: 6 months ]
    The rate of tumor-associated complications (bowel obstruction, bleeding etc) during neoadjuvant chemotherapy

  8. Sphincter preservation rate [ Time Frame: 1 month ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04135313


Locations
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Russian Federation
N.N.Blokhin Russian Cancer Research Center
Moscow, Russian Federation, 115478
Sponsors and Collaborators
Blokhin's Russian Cancer Research Center
Investigators
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Principal Investigator: Zaman Z Mamedli, PhD N.N.Blokhin Russian Cancer Research Center
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Responsible Party: Sergey Gordeyev, Principal Investigator, Consultant surgeon, Blokhin's Russian Cancer Research Center
ClinicalTrials.gov Identifier: NCT04135313    
Other Study ID Numbers: RuCorT-03
First Posted: October 22, 2019    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sergey Gordeyev, Blokhin's Russian Cancer Research Center:
rectal cancer
induction chemotherapy
consolidation chemotherapy
neoadjuvant chemotherapy
Additional relevant MeSH terms:
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Rectal Neoplasms
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents