Clinical trial NCT04170530: Neoadjuvant mFOLFOXIRI Chemotherapy Alone for Extramural Vascular Invasion Positive Locally Advanced Rectal Cancer
Official title: Neoadjuvant mFOLFOXIRI Chemotherapy Alone for Extramural Vascular Invasion(EMVI) Positive Rectal Cancer: A Phase II, Single-arm, Prospective Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: Extramural Vascular Invasion
Neoadjuvant
chemotherapy
mFOLFOXIRI
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2019-11-20
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC.

Detailed description: It is an investigator-initiated, single institution, prospective, single-arm clinical study to evaluate the efficacy and safety of FOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC.Patients of LARC with EMVI+ evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All EMVI+ LARC will receive the study regimen every 2 weeks for 6 cycles. MRI will be performed after 3 cycles of chemotherapy to assess clinical response.MRI was performed to assess clinical response after chemotherapy. 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).If the tumor response is good enough(partial response or complete response), the patient will receive another 3 cycles of FOLFOXIRI 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. All patients will receive 6 cycles of mFOLFOX6 or 4 cycles XELOX as adjuvant chemotherapy after TME.

Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 18 to 75 years at diagnosis;
2. ECOG status 0 or 1;
3. Signed informed consent; able to comply with study and/or follow- up procedures;
4. Diagnosis of rectal adenocarcinoma;
5. Distal border of the tumor must be located \< 12 cm from the anal verge;
6. MRI examination diagnosed EMVI-positive;
7. Tumor amenable to curative resection;
8. 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.
9. No renal disease that would preclude study treatment or follow-up

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: Three years
Secondary outcomes:
measure: Tumor downstaging rate
timeFrame: 2 years
measure: pCR
timeFrame: 2 years
measure: R0 rate
timeFrame: 2 years
measure: locoregional recurrence
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: