Neoadjuvant mFOLFOXIRI Chemotherapy Alone for Extramural Vascular Invasion Positive Locally Advanced Rectal Cancer

Sponsor

First Affiliated Hospital of Zhejiang University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04170530

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

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 mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Drug: mFOLFOXIRI	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

51 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant mFOLFOXIRI Chemotherapy Alone for Extramural Vascular Invasion(EMVI) Positive Rectal Cancer: A Phase II, Single-arm, Prospective Clinical Study

Actual Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Nov 1, 2020

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mFOLFOXIRI patients received FOLFOXIRI alone for 6 cycles before surgery.	Drug: mFOLFOXIRI irinotecan* 135 mg/m² + oxaliplatin 68 mg/m² + leucovorin 400 mg/m² + 5-FU 2400 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle Other Names: 5-FU Oxaliplatin Irinotecan

Arm

Intervention/Treatment

Experimental: mFOLFOXIRI

patients received FOLFOXIRI alone for 6 cycles before surgery.

Drug: mFOLFOXIRI

irinotecan* 135 mg/m² + oxaliplatin 68 mg/m² + leucovorin 400 mg/m² + 5-FU 2400 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle

Other Names:

5-FU

Oxaliplatin

Irinotecan

Outcome Measures

Primary Outcome Measures

MFS [Three years]
metastasis free survival

Secondary Outcome Measures

Tumor downstaging rate [2 years]
the proportion of tumor downstaging to ypT0-2N0M0
pCR [2 years]
Pathologic complete response rate
R0 rate [2 years]
R0 resection rate
locoregional recurrence [3 years]
The rate of local recurrence
DFS [3 years]
disease-free survival
OS [5 years]
overall survival.
Reported Adverse events [2 years]
The incidence of >=3 grade adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged ≥ 18 to 75 years at diagnosis;
ECOG status 0 or 1;
Signed informed consent; able to comply with study and/or follow- up procedures;
Diagnosis of rectal adenocarcinoma;
Distal border of the tumor must be located < 12 cm from the anal verge;
MRI examination diagnosed EMVI-positive;
Tumor amenable to curative resection;
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

Exclusion Criteria:

Hypersensitivity to fluorouracil, oxaliplatin or irinotecan;
Patient had received pelvic radiotherapy;
Patient had received systemic chemotherapy;
History of invasive colon or rectal malignancy, regardless of disease-free interval;
Had metastatic disease;
Patient had second malignant disease within 5 years;
Uncontrolled co-morbid illnesses or other concurrent disease;
Patients refused to signed informed consent.
Pregnant and Nursing women;