Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer

Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer：an Open-label, Single-arm, Multicenter Phase II Study

To evaluate the efficacy and safety of neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) in the patients with resectable liver metastasis of colorectal cancer

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms; Drug Therapy
• Intervention / Treatment: Drug: FOLFOXIRI

Detailed Description

For the patients Neoadjuvant FOLFOX chemotherapy is recommended for the resectable liver metastasis colorectal cancer. Neoadjuvant chemotherapy could suppress tumor, reduce metastasis, inhibit recurrence and improve long-term prognosis. Moreover, neoadjuvant chemotherapy could provide evidence about tumor response to drugs for the adjuvant chemotherapy. Furthermore, according to the biological behavior of tumors observed by neoadjuvant chemotherapy, unnecessarily excessive surgery could be avoided. However, some studies suggested that drug efficiency was consistent with resection rate. And FOLFOXIRI has been observed efficacy in the treatment of metastatic colorectal cancer with manageable toxicities. Therefore, we evaluate the efficacy and safety of neoadjuvant FOLFOXIRI chemotherapy in the patients with resectable liver metastasis of colorectal cancer to achieve higher resection rate and longer survival.

In this prospective study, 30 patients with resectable colorectal liver metastases were treated with neoadjuvant FOLFOXIRI chemotherapy. After 4 cycles of neoadjuvant chemotherapy, the liver metastases will be removed. If there are primary bowel lesions, they will be resected together. Safety profile was recorded based on NCI Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0). Objective response was evaluated by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Before treatment and after 4 cycles of neoadjuvant chemotherapy, we will evaluate tumor metabolic response via FDG-PET and monitor the dynamic changes of peripheral blood ctDNA.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuanhe Wang, Doctor; Phone Number: 18900918737; Email: wangyuanhe@sina.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Recruiting
      • Liaoning Cancer Hospital
      • Contact: Yuanhe Wang; Phone Number: 18900918737; Email: wangyuanhe@sina.com
      • Principal Investigator: Jingdong Zhang

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

• Age: 18-75years old
• Histologically confirmed colorectal cancer with liver metastasis (all patients should have the pathological report of colorectal cancer). The chances of hepatocellular carcinoma or metastasis from other primary lesions should be excluded.
• It was confirmed by imaging that the liver metastases and the primary intestinal lesions were all resectable.
• Radical resection of colorectal cancer after adjuvant chemotherapy complete 1 years later with liver metastases.
• There is at least one measurable objective tumor of the tumor (according to the 1.1 version of RECIST standard).
• Liver metastases can be excised by R0 and sufficient normal liver tissue can be retained
• ECOG status: 0～1
• Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

Neutrophil count≥1.5×10^9/L Platelet count≥90×10^9/L Hemoglobin≥90g/L Total bilirubin (TBI) ≤ 1.5 * ULN Alanine aminotransferase (ALT)≤2.5 * ULN Aspartate aminotransferase (AST)≤2.5 * ULN Alkaline phosphatase (ALP)≤2.5 * ULN

- Signed informed consent; able to comply with study and/or follow- up procedures

Exclusion Criteria:

• Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
• In addition to liver metastases, there are other parts of metastasis
• Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; Active ischemic heart disease; Myocardial infarction within the past 6 months; Symptomatic arrhythmia Uncontrolled hypertension. Unexplained syncope occurred within 3 months
• Gastric ulcers or duodenal ulcers for the treatment of resistance;
• 3 or 4 grade gastrointestinal bleeding / bleeding;
• Gastrointestinal perforation / fistula;
• Abdominal abscess;
• Infectious or inflammatory bowel disease
• HIV infection and/or active hepatitis B virus infection
• Pregnant or lactating women. Fertile patients must use effective contraception
• Any serious acute or chronic disease that can not be involved in the study or to influence the interpretation of the results of the study
• Other intervention clinical trials were combined at the same time.
• Nerve or mental abnormality affecting cognitive ability
• Other malignancy except effectively treated squamous cell or basal cell skin cancer,
• Other situations that the researchers think should be excluded.

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: FOLFOXIRI; Patients received 4 cycles of neoadjuvant FOLFOXIRI chemotherapy before surgical resection.	Drug: FOLFOXIRI; IRINOTECAN 150 mg/m^2 IV over 1-h, day 1 + OXALIPLATIN 85 mg/m^2 IV over 2-h, day 1 + L-LEUCOVORIN 200 mg/m^2 IV over 2-h, day 1 + 5-FLUOROURACIL 2800 mg/m^2 IV 48-h continuous infusion, starting on day 1 administered every two weeks for 4 cycles (2 months).; Other Names: Irinotecan; 5-Fluorouracil; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ratio of tumor downstaging to stage 0 and stage I	Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor regression grade (TRG)	The level of tumor regression under pathological examination	2 years
Disease free survival	Estimated from the date of surgery to the date of recurrence.	3 years
Overall survival time	Estimated from the date of enrollment to death from any cause.	3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	The grade of toxicity will be assessed using the NCI-CTCAE version 4.0.	3 years
ctDNA assessment and relation to clinical outcome	The relationship between ctDNA and survival will be evaluated.	3 years
SUVmax assessment and relation to clinical outcome	Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy	At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days)
Quality of life (QLQ C30)	Scores according to EORTC QLQ-C30 scoring manual	Every 2 weeks after the first treatment until 3 years

Collaborators and Investigators

• Sponsor: China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: March 24, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 4, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Oxaliplatin; Irinotecan
• Other Study ID Numbers: LGIOG-2017-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No