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

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

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.

Study Overview

• Status: Unknown
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: mFOLFOXIRI

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 Type: Interventional
• Enrollment (Anticipated): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Recruiting
      • The first Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Hua Hanju, M.D; Phone Number: 87236858 +86 15088779188; Email: tomorrow97@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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; Irinotecan; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MFS	metastasis free survival	Three years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: chemotherapy; Neoadjuvant; Extramural Vascular Invasion; mFOLFOXIRI
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Oxaliplatin; Irinotecan
• Other Study ID Numbers: TRICHEMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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