Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer

Colorectal Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03487939
• Other study ID #: LGIOG-2017-03
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2018
• Est. completion date: October 1, 2021

Study information

• Verified date: April 2021
• Source: China Medical University, China
• Contact: Yuanhe Wang, Doctor
• Phone: 18900918737
• Email: wangyuanhe[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Drug Therapy

Intervention

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).

Locations

Country	Name	City	State
China	Liaoning cancer hospital	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Tumor regression grade (TRG)	The level of tumor regression under pathological examination	2 years
Secondary	Disease free survival	Estimated from the date of surgery to the date of recurrence.	3 years
Secondary	Overall survival time	Estimated from the date of enrollment to death from any cause.	3 years
Secondary	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
Secondary	ctDNA assessment and relation to clinical outcome	The relationship between ctDNA and survival will be evaluated.	3 years
Secondary	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)
Secondary	Quality of life (QLQ C30)	Scores according to EORTC QLQ-C30 scoring manual	Every 2 weeks after the first treatment until 3 years