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

Locally Advanced Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04423965
• Other study ID #: TRICHEMO
• Status: Recruiting
• Phase: Phase 2
• Start date: May 12, 2020
• Est. completion date: May 1, 2025

Study information

• Verified date: March 2021
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Guosheng Wu, MD
• Phone: +8617857310313
• Email: guosheng_wu[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

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

Combination Product:
• Chemoradiotherapy
Capecitabine based chemoradiotherapy

Locations

Country	Name	City	State
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (3)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University	First Affiliated Hospital of Wenzhou Medical University, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MFS	metastasis free survival	3 years
Secondary	Tumor downstaging rate	the proportion of tumor downstaging to ypT0-2N0M0	2 years
Secondary	pCR	Pathologic complete response rate	2 years
Secondary	RFS	recurrence-free survival	3 years
Secondary	DFS	disease-free survival	3 years
Secondary	OS	overall survival	5 years
Secondary	Reported Adverse events	The incidence of >=3 grade adverse events	2 years