Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer

Phase 2

Recruiting

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

• Registration Number: NCT05378919
• Lead Sponsor: Lithuanian University of Health Sciences

Brief Summary

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

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 Timeline

• Study Start: 2015-06-01
• Status Verified: 2022-05
• Study First Submitted: 2022-05-08
• Study First Submitted QC: 2022-05-12
• Last Update Submitted: 2022-05-12
• Study First Posted: 2022-05-18
• Last Update Posted: 2022-05-18
• Primary Completion: 2025-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (Control): Radiotherapy + fluorouracil	Fluorouracil/folic acid	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.
Arm A (Control): Radiotherapy + fluorouracil	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) , 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.
Arm B (Experimental): Chemotherapy with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4) regimen	Chemotherapy in regimen with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4)	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).
Arm B (Experimental): Chemotherapy with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4) regimen	Radiotherapy 50 Gy	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).

Primary Outcome Measures

Name	Time	Method
disease-free survival	3 year	To compare the 3-year disease-free survival between the investigational arm and the control arm.

Secondary Outcome Measures

Name	Time	Method
Overall survival	7 year	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.

Trial Locations

Locations (1)

Rita Ambraziene; 🇱🇹 Kaunas, Lithuania