Clinical trial NCT03487939: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Neoplasms
Drug Therapy
Lead sponsor: China Medical University, China
Sponsor class: OTHER
First posted: 2018-04-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The ratio of tumor downstaging to stage 0 and stage I
timeFrame: 2 years
Secondary outcomes:
measure: Tumor regression grade (TRG)
timeFrame: 2 years
measure: Disease free survival
timeFrame: 3 years
measure: Overall survival time
timeFrame: 3 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 3 years
measure: ctDNA assessment and relation to clinical outcome
timeFrame: 3 years
measure: SUVmax assessment and relation to clinical outcome
timeFrame: At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days)
measure: Quality of life (QLQ C30)
timeFrame: Every 2 weeks after the first treatment until 3 years
Other outcomes:
Locations:
city: Shenyang
country: China
facility: Liaoning cancer hospital
state: Liaoning
Study officials:
References: