Clinical trial NCT04423965: A Trial of Neoadjuvant mFOLFOXIRI Versus CRT in the EMVI Positive LARC
Official title: A Multicenter Randomized Controlled Phase II Trial of Neoadjuvant mFOLFOXIRI Versus Routine Chemoradiotherapy in the EMVI Positive Locally Advanced Rectal Cancer (TRICHEMO)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Wenzhou Medical University
name: Zhejiang Cancer Hospital
First posted: 2020-06-09
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MFS
timeFrame: 3 years
Secondary outcomes:
measure: Tumor downstaging rate
timeFrame: 2 years
measure: pCR
timeFrame: 2 years
measure: RFS
timeFrame: 3 years
measure: DFS
timeFrame: 3 years
measure: OS
timeFrame: 5 years
measure: Reported Adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: