A Trial of Neoadjuvant mFOLFOXIRI Versus CRT in the EMVI Positive LARC

NCT ID: NCT04423965

Last Updated: 2021-03-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-12
• Study Completion Date: 2025-05-01

Brief Summary

Extramural Vascular Invasion Positive(EMVI+) is a high risk of distant metastasis for locally advanced rectal cancer(LARC) after resection. The study is to evaluate the efficacy and safety of FOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC in contrast to the efficacy of standard Chemoradiotherapy (CRT).

Detailed Description

It is an investigator-initiated, multicentered, randomized controlled clinical study to evaluate the efficacy and safety of mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC in contrast to standard chemoradiotherapy. Patients of LARC with EMVI+ evaluated by pelvic magnetic resonance imaging (MRI) are enrolled in this trial. All patients will be randomized divided into two groups.

Experimental group will receive 3 cycles of mFOLFOXIRI, followed to be performed MRI to assess clinical response. If the tumor response is good enough (partial response or complete response), the patient will receive another 3 cycles of mFOLFOXIRI then surgery. On the contrary, if the tumor shows poor response (stable disease or progressive disease) or with mesorectal fascia-positive or ycT4a/b after re-evaluation, radiotherapy will be performed combined with capecitabine before operation. Control group will receive standard capecitabine based chemoradiotherapy.

Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). All patients will receive 4 cycles of XELOX as adjuvant chemotherapy after TME.

Conditions

Locally Advanced Rectal Cancer

Study Design

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

Study Groups

mFOLFOXIRI

Patients receive 6 cycles of mFOLFOXIRI

Group Type: EXPERIMENTAL

mFOLFOXIRI

Intervention Type: DRUG

irinotecan 165 mg/m² IV day 1+ oxaliplatin 85 mg/m² IV day 1 + leucovorin 400 mg/m² day 1, fluorouracil 1200mg/m²/day \*2 days (total 2400 mg/m² over 48 hours) continuous infusion starting on day 1 of each 2 weeks cycle

Chemoradiotherapy(CRT)

Patients receive standard chemoradiotherapy

Group Type: EXPERIMENTAL

Chemoradiotherapy

Intervention Type: COMBINATION_PRODUCT

Capecitabine based chemoradiotherapy

Interventions

mFOLFOXIRI

irinotecan 165 mg/m² IV day 1+ oxaliplatin 85 mg/m² IV day 1 + leucovorin 400 mg/m² day 1, fluorouracil 1200mg/m²/day \*2 days (total 2400 mg/m² over 48 hours) continuous infusion starting on day 1 of each 2 weeks cycle

Intervention Type: DRUG

Chemoradiotherapy

Capecitabine based chemoradiotherapy

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. Aged ≥ 18 to 70 years at diagnosis;

2. ECOG status 0-2;

3. Diagnosis of rectal adenocarcinoma(Distal border of the tumor must be located < 12 cm from the anal verge);

4. MRI examination diagnosed EMVI-positive;

5. Tumor amenable to curative resection;

6. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: (1) Neutrophilic granulocytes ≥ 3.0 x10^9/L, Platelet count ≥ 75 x 10^9/L, Hemoglobin (Hb) ≥ 90g/L; (2) bilirubin ≤1.5 x the upper limit of normal (ULN),Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) ≤ 2.5 x ULN; (3) Serum creatinine ≤ 1.5 x ULN.No renal disease that would preclude study treatment or follow-up

7. Signed informed consent; able to comply with study and/or follow- up procedures

Exclusion Criteria

1. Hypersensitivity to fluorouracil, oxaliplatin or irinotecan;

2. Patient had received pelvic radiotherapy;

3. Patient had received systemic chemotherapy;

4. History of invasive colon or rectal malignancy, regardless of disease-free interval;

5. Had metastatic disease;

6. Patient had second malignant disease within 5 years;

7. Uncontrolled co-morbid illnesses or other concurrent disease;

8. Patients refused to signed informed consent.

9. Pregnant and Nursing women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Guosheng Wu

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Guosheng Wu, MD

Role: CONTACT

guosheng_wu@zju.edu.cn

+8617857310313 ext. 87236858

Weiqin Jiang, MD

Role: CONTACT

1312028@zju.edu.cn

+8615068117618 ext. 87236858

Facility Contacts

Guosheng Wu, MD

Role: primary

guosheng_wu@zju.edu.cn

+8617857310313 ext. 87236858

Other Identifiers

TRICHEMO

Identifier Type: -

Identifier Source: org_study_id