Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer

NCT ID: NCT05378919

Last Updated: 2022-05-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-01
• Study Completion Date: 2027-06-01

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.

Conditions

Neoadjuvant Therapy in Rectal Cancer, Radiotherapy, FOLFOX

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Radiotherapy 50 Gy

Intervention Type: RADIATION

Radiotherapy 50 Gy 5 radiations per week of 2 Gy for 5 weeks

Fluorouracil/folic acid

Intervention Type: DRUG

Fluorouracil 400 mg/m² D1-4 and folic acid 20mg/m2 D1-4 the first and fifth weeks of radiotherapy

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).

Group Type: EXPERIMENTAL

Chemotherapy in regimen with Oxaliplatin, fluorouracil, folinic acid (FOLFOX4)

Intervention Type: DRUG

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).

Radiotherapy 50 Gy

Intervention Type: RADIATION

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.

Interventions

Radiotherapy 50 Gy

Radiotherapy 50 Gy 5 radiations per week of 2 Gy for 5 weeks

Intervention Type: RADIATION

Fluorouracil/folic acid

Fluorouracil 400 mg/m² D1-4 and folic acid 20mg/m2 D1-4 the first and fifth weeks of radiotherapy

Intervention Type: 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).

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lithuanian University of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Rita Ambraziene

Sub-Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rita Ambraziene

Kaunas, , Lithuania

Site Status: RECRUITING

Countries

Lithuania

Central Contacts

Rita Ambraziene

Role: CONTACT

rita.ambraziene@gmail.com

+37037326196

Facility Contacts

Rita Ambraziene

Role: primary

rita.ambraziene@gmail.com

837326196

Role: backup

rita.ambraziene@gmail.com

Other Identifiers

RECTUM2015

Identifier Type: -

Identifier Source: org_study_id