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

A Multicenter Randomized Controlled Phase II Trial of Neoadjuvant mFOLFOXIRI Versus Routine Chemoradiotherapy in the EMVI Positive Locally Advanced Rectal Cancer (TRICHEMO)

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).

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: mFOLFOXIRI; Combination product: Chemoradiotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Guosheng Wu, MD; Phone Number: 87236858 +8617857310313; Email: guosheng_wu@zju.edu.cn
• Study Contact Backup: Name: Weiqin Jiang, MD; Phone Number: 87236858 +8615068117618; Email: 1312028@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Guosheng Wu, MD; Phone Number: 87236858 +8617857310313; Email: guosheng_wu@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Experimental: mFOLFOXIRI; Patients receive 6 cycles of mFOLFOXIRI	Drug: 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
Experimental: Chemoradiotherapy(CRT); Patients receive standard chemoradiotherapy	Combination product: Chemoradiotherapy; Capecitabine based chemoradiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MFS	metastasis free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor downstaging rate	the proportion of tumor downstaging to ypT0-2N0M0	2 years
pCR	Pathologic complete response rate	2 years
DFS	disease-free survival	3 years
Reported Adverse events	The incidence of >=3 grade adverse events	2 years
OS	overall survival	5 years
RFS	recurrence-free survival	3 years

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; First Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2020
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 21, 2021
• Last Verified: March 1, 2021

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
• Other Study ID Numbers: TRICHEMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes