Neoadjuvant FOLFOXIRI Chemotherapy in Patients With Locally Advanced Colon Cancer

Neoadjuvant FOLFOXIRI (Irinotecan, Oxaliplatin and Fluorouracil) Chemotherapy in Patients With Locally Advanced Colon 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 locally advanced colon cancer.

Study Overview

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

Detailed Description

For the patients with locally advanced colon cancer, adjuvant FOLFOX and XELOX chemotherapy have become standard treatment. However, 30% - 40% patients suffered from local recurrence or distant metastasis after this standard treatment. Neoadjuvant chemotherapy could shrink tumors, eliminate micrometastasis, reduce surgical trauma and accelerate recovery. Hence, we evaluate the efficacy and safety of FOLFOXIRI as neoadjuvant chemotherapy in treating patients with locally advanced colon cancer.

In this prospective study, 30 patients with locally advanced colon cancer will be treated with 4 cycles of neoadjuvant FOLFOXIRI chemotherapy followed by surgical resection. PET-CT scanning will be performed before and after the neoadjuvant FOLFOXIRI chemotherapy to assess SUVmax changes. The ctDNA in peripheral blood before and after each cycle of neoadjuvant FOLFOXIRI chemotherapy will be detected. In the course of treatment, safety evaluation will be carried out according to adverse reaction classification (CTCAE) 4. 0.

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

Contacts and Locations

• Study Contact: Name: Jingdong Zhang; Phone Number: +86-13804027878; Email: zhangjingdong@cancerhosp-ln-cmu.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Recruiting
      • Liaoning cancer hospital
      • Principal Investigator: Jingdong Zhang
      • Contact: Yuanhe Wang; Email: wangyuanhe@sina.comm

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Age: 18-75years old
• Primary and pathological diagnosis of colon adenocarcinoma
• Radiographic evaluation of initial resectable colon cancer
• T4b colon cancer
• 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:

• Previous treatment with oxaliplatin, irinotecan or fluorouracil
• Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
• With distant 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
• Digestive system diseases that would preclude study treatment or follow-up within the past 6 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 1h, day 1 + Oxaliplatin 85 mg/m^2 IV over 2h, day 1 + L-Leucovorin 200 mg/m^2 IV over 2h, day 1 + 5-Fluorouracil 2800 mg/m^2 IV 48h 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
Quality of life (QLQ C30)	Scores according to EORTC QLQ-C30 scoring manual	Every 2 weeks after the first treatment until 3 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
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The grade of toxicity will be assessed using the NCI-CTCAE version 4.0	3 years
ctDNA change	The relationship between ctDNA and survival will be evaluated	3 years
SUVmax changes	Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy	At the begin of Cycle 1 and the end of Cycle 4 (each cycle is 14 days)

Collaborators and Investigators

• Sponsor: China Medical University, China
• Investigators: Study Chair: Jingdong Zhang, Cancer Hospital of China Medical University, Department of Medical Oncology, Liaoning Cancer Hospital & Institute

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (Actual): March 30, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 14, 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; Colorectal Neoplasms; Colonic 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-2017-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No