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Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer

Primary Purpose

Colorectal Neoplasms, Drug Therapy

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
FOLFOXIRI
Sponsored by
China Medical University, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Liaoning cancer hospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFOXIRI

Arm Description

Patients received 4 cycles of neoadjuvant FOLFOXIRI chemotherapy before surgical resection.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Tumor regression grade (TRG)
The level of tumor regression under pathological examination
Disease free survival
Estimated from the date of surgery to the date of recurrence.
Overall survival time
Estimated from the date of enrollment to death from any cause.
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.
ctDNA assessment and relation to clinical outcome
The relationship between ctDNA and survival will be evaluated.
SUVmax assessment and relation to clinical outcome
Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy
Quality of life (QLQ C30)
Scores according to EORTC QLQ-C30 scoring manual

Full Information

First Posted
March 24, 2018
Last Updated
April 13, 2021
Sponsor
China Medical University, China
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1. Study Identification

Unique Protocol Identification Number
NCT03487939
Brief Title
Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer
Official Title
Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer：an Open-label, Single-arm, Multicenter Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
October 1, 2021 (Anticipated)
Study Completion Date
October 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
China Medical University, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms, Drug Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FOLFOXIRI
Arm Type
Experimental
Arm Description
Patients received 4 cycles of neoadjuvant FOLFOXIRI chemotherapy before surgical resection.
Intervention Type
Drug
Intervention Name(s)
FOLFOXIRI
Other Intervention Name(s)
Irinotecan, Oxaliplatin, 5-Fluorouracil
Intervention Description
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).
Primary Outcome Measure Information:
Title
The ratio of tumor downstaging to stage 0 and stage I
Description
Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Tumor regression grade (TRG)
Description
The level of tumor regression under pathological examination
Time Frame
2 years
Title
Disease free survival
Description
Estimated from the date of surgery to the date of recurrence.
Time Frame
3 years
Title
Overall survival time
Description
Estimated from the date of enrollment to death from any cause.
Time Frame
3 years
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
The grade of toxicity will be assessed using the NCI-CTCAE version 4.0.
Time Frame
3 years
Title
ctDNA assessment and relation to clinical outcome
Description
The relationship between ctDNA and survival will be evaluated.
Time Frame
3 years
Title
SUVmax assessment and relation to clinical outcome
Description
Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy
Time Frame
At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days)
Title
Quality of life (QLQ C30)
Description
Scores according to EORTC QLQ-C30 scoring manual
Time Frame
Every 2 weeks after the first treatment until 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuanhe Wang, Doctor
Phone
18900918737
Email
wangyuanhe@sina.com
Facility Information:
Facility Name
Liaoning cancer hospital
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuanhe Wang
Phone
18900918737
Email
wangyuanhe@sina.com
First Name & Middle Initial & Last Name & Degree
Jingdong Zhang

12. IPD Sharing Statement

Learn more about this trial

Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer

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