Neoadjuvant FOLFOXIRI Chemotherapy in Resectable Liver Metastasis of Colorectal Cancer：an Open-label, Single-arm, Multicenter Phase II Study
Overview
- Phase
- Phase 2
- Intervention
- FOLFOXIRI
- Conditions
- Colorectal Neoplasms
- Sponsor
- China Medical University, China
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- The ratio of tumor downstaging to stage 0 and stage I
- Last Updated
- 5 years ago
Overview
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.
Investigators
Jingdong Zhang
Director
China Medical University, China
Eligibility Criteria
Inclusion Criteria
- Not provided
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
Arms & Interventions
FOLFOXIRI
Patients received 4 cycles of neoadjuvant FOLFOXIRI chemotherapy before surgical resection.
Intervention: FOLFOXIRI
Outcomes
Primary Outcomes
The ratio of tumor downstaging to stage 0 and stage I
Time Frame: 2 years
Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I
Secondary Outcomes
- Tumor regression grade (TRG)(2 years)
- Overall survival time(3 years)
- Disease free survival(3 years)
- ctDNA assessment and relation to clinical outcome(3 years)
- SUVmax assessment and relation to clinical outcome(At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days))
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(3 years)
- Quality of life (QLQ C30)(Every 2 weeks after the first treatment until 3 years)