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

• Sponsor: First Affiliated Hospital of Zhejiang University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04423965
• Collaborator: First Affiliated Hospital of Wenzhou Medical University (Other), Zhejiang Cancer Hospital (Other)
• Enrollment: 220
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 59.6
• Patients Per Site Per Month: 3.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Drug: mFOLFOXIRI; Combination Product: Chemoradiotherapy	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Randomized Controlled Phase II Trial of Neoadjuvant mFOLFOXIRI Versus Routine Chemoradiotherapy in the EMVI Positive Locally Advanced Rectal Cancer (TRICHEMO)
• Actual Study Start Date: May 12, 2020
• Anticipated Primary Completion Date: May 1, 2022
• Anticipated Study Completion Date: May 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. MFS [3 years]

   metastasis free survival

Secondary Outcome Measures

1. Tumor downstaging rate [2 years]

   the proportion of tumor downstaging to ypT0-2N0M0

2. pCR [2 years]

   Pathologic complete response rate

3. RFS [3 years]

   recurrence-free survival

4. DFS [3 years]

   disease-free survival

5. OS [5 years]

   overall survival

6. Reported Adverse events [2 years]

   The incidence of >=3 grade adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310006

Sponsors and Collaborators

• First Affiliated Hospital of Zhejiang University
• First Affiliated Hospital of Wenzhou Medical University
• Zhejiang Cancer Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Guosheng Wu, Chief physician, First Affiliated Hospital of Zhejiang University
• ClinicalTrials.gov Identifier: NCT04423965
• Other Study ID Numbers: TRICHEMO
• First Posted: Jun 9, 2020
• Last Update Posted: Mar 23, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Rectal Neoplasms

Study Results

No Results Posted as of Mar 23, 2021