Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer (RECTUM2015)

Evaluation and Comparison of the Efficacy of a New Standard Pre-operative Chemotherapy for Stage II and III Colorectal Cancer According to the FOLFOX4 Regimen With Routine Chemoradiation Therapy

Phase II, Multicenter, Open-label, Randomized Study evaluating neoadjuvant chemotherapy (FOLFOX4) in patients with stage II and III colorectal cancer with standard chemoradiation Defined by Magnetic Resonance Imaging

Study Overview

• Status: Recruiting
• Conditions: Neoadjuvant Therapy in Rectal Cancer, Radiotherapy, FOLFOX
• Intervention / Treatment: Radiation: Radiotherapy 50 Gy; Drug: Fluorouracil/folic acid; Radiation: Radiotherapy 50 Gy; Drug: Chemotherapy in regimen with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4)

Detailed Description

This is a biomedical research, phase II, multicenter, open-label, randomized study, comparing neoadjuvant CT with FOLFOX4, versus immediate preoperative chemoradiotherapy (CRT), in patients with locally advanced rectal cancer. Randomization in a 1: 1 ratio, neoadjuvant chemotherapy or chemoradiation. The purpose of the study is to evaluate the efficacy, tolerability, and comparability of new standard preoperative chemotherapy with FOLFOX4 in patients with stage II and III colorectal cancer compared to routine chemoradiation.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rita Ambraziene; Phone Number: +37037326196; Email: rita.ambraziene@gmail.com

Study Locations

• Lithuania
  • Kaunas, Lithuania, 45304
    • Recruiting
    • Rita Ambraziene
    • Contact: Rita Ambraziene; Phone Number: 837326196; Email: rita.ambraziene@gmail.com
    • Contact: Email: rita.ambraziene@gmail.com
    • Principal Investigator: Rita Ambraziene, MD
    • Principal Investigator: Rasa Jančiauskienė, prof
    • Sub-Investigator: Tadas Latkauskas, prof
    • Sub-Investigator: Laimonas Jaruševičius, assoc.prof
    • Sub-Investigator: Algimantas Tamelis, prof
    • Sub-Investigator: Žilvinas Saladžinskas, prof
    • Sub-Investigator: Irina Gineikienė, phd
    • Sub-Investigator: Ingrida Pikūnienė, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• diagnosed with rectal adenocarcinoma;
• radiologically measurable tumor size;
• general condition (ECOG 0-2 points);
• stage II or III rectal tumor clinically (pelvic MRI and endorectal ultrasound),
• in the absence of long-term spread of the disease (confirmed by radiological examinations (computed tomography of the thorax and abdomen));
• during preoperative proctoscopy, the tumor is detected 0 -15 cm from the anus;
• Blood tests 28 days before the start of treatment:

and general blood count: neutrophils greater than 1.5x10 9 / l, platelets greater than 100 x 10 9 / l, Hemoglobin greater than 80 g / l, liver enzymes (Aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT) not more than 3 times upper limit), and renal function (creatinine up to 1.5 times the upper limit of normal) is normal; women of childbearing potential - negative pregnancy test;

• A signed informed consent form.

Exclusion Criteria:

• patients with signs of intestinal obstruction at the start of treatment;
• previous lower abdominal radiation therapy;
• other tumors over a five-year period;
• pregnant or breastfeeding women;
• men and women of childbearing potential who do not agree to use adequate contraception;
• Patient co-morbidities that would make the patient unsuitable for this study or significantly interfere with the assessment of safety and toxicity.

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
Active Comparator: Arm A (Control): Radiotherapy + fluorouracil; Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session; 25 fractions) + fluorouracil/leucovorin 400 mg/m² 1-4 day the first and fifth weeks of radiotherapy) , then 6-8 weeks after chemoradiation, surgery, followed by adjuvant chemotherapy for 4-6 months, either Folfox4 or fluorouracil, depending on the center's choice.	Radiation: Radiotherapy 50 Gy; Radiotherapy 50 Gy 5 radiations per week of 2 Gy for 5 weeks; Drug: Fluorouracil/folic acid; Fluorouracil 400 mg/m² D1-4 and folic acid 20mg/m2 D1-4 the first and fifth weeks of radiotherapy; Radiation: Radiotherapy 50 Gy; Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session; 25 fractions) + fluorouracil/leucovorin 400 mg/m² 1-4 day the first and fifth weeks of radiotherapy. FOLOFX4 will be administrated for 8 cycles over a 16 week period. Patients will undergo re-staging within 6 weeks of their 8th cycle of FOLFOX. This will include MRI of the pelvis. If the reassessment reveals that there has been no disease progression compared to the pre-treatment evaluation and the patient remains a candidate for an R0 resection, the patient will proceed to definitive rectal cancer surgery within 8 weeks from the last chemotherapy dose. If the surgical oncologist's reassessment reveals that the patient is not a candidate for an R0 resection, the patient will proceed to standard pre-operative radiation with synchronous fluorouracil.
Experimental: Arm B (Experimental): Chemotherapy with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4) regimen; Neoadjuvant CT FOLFOX4, 8 cycles (ca. 4 months; each cycle = 2 weeks): oxaliplatin: 85 mg/m² in 2 hours at D1; folinic acid: 100 mg/m² simultaneously in 2 hours at D1 and D2 during the Oxaliplatin; bolus 5-fluorouracil (5-FU) 400mg/m² D1+D2; infusion 5-fluorouracil (5-FU): 600 mg/m² continuous infusion during 22hours at D1 and D2, every 14 days during 42 months (8 cycles).	Radiation: Radiotherapy 50 Gy; Radiotherapy 50 Gy 5 radiations per week of 2 Gy for 5 weeks; Radiation: Radiotherapy 50 Gy; Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session; 25 fractions) + fluorouracil/leucovorin 400 mg/m² 1-4 day the first and fifth weeks of radiotherapy. FOLOFX4 will be administrated for 8 cycles over a 16 week period. Patients will undergo re-staging within 6 weeks of their 8th cycle of FOLFOX. This will include MRI of the pelvis. If the reassessment reveals that there has been no disease progression compared to the pre-treatment evaluation and the patient remains a candidate for an R0 resection, the patient will proceed to definitive rectal cancer surgery within 8 weeks from the last chemotherapy dose. If the surgical oncologist's reassessment reveals that the patient is not a candidate for an R0 resection, the patient will proceed to standard pre-operative radiation with synchronous fluorouracil.; Drug: Chemotherapy in regimen with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4); oxaliplatin: 85 mg/m² in 2 hours at D1; folinic acid: 100 mg/m² simultaneously in 2 hours at D1 and D2 during the Oxaliplatin; bolus 5-fluorouracil (5-FU) 400mg/m² D1+D2; infusion 5-fluorouracil (5-FU): 600 mg/m² continuous infusion during 22hours at D1 and D2, every 14 days during 42 months (8 cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival	To compare the 3-year disease-free survival between the investigational arm and the control arm.	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival will be defined as the time from randomisation to the time of occurrence of the first death regardless to its cause. Patients alive at the time of analysis will be censored at the date of the last follow up.	7 year

Collaborators and Investigators

• Sponsor: Lithuanian University of Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2027

Study Registration Dates

• First Submitted: May 8, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Hematinics; Fluorouracil; Oxaliplatin; Leucovorin; Levoleucovorin; Folic Acid
• Other Study ID Numbers: RECTUM2015

Drug and device information, study documents

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