Clinical trial NCT05362825: Surgery Outcome Treated by Neo-adjuvant Combination of Oxaliplatin, Irinotecan, Folinic Acid and Fluorouracil (FOLFOXIRI) Regimen in Synchronous Liver Limited Metastasis Colorectal Cancer
Official title: Surgery Outcome Treated by Neo-adjuvant Chemotherapy FOLFOXIRI Regimen in Colorectal Cancer With Liver-limited Synchronous Metastases
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Metastasis Colon Cancer
Synchronous Neoplasm
Keywords: FOLFOXIRI
Lead sponsor: Cho Ray Hospital
Sponsor class: OTHER
Collaborators: name: University of Medicine and Pharmacy at Ho Chi Minh City
First posted: 2022-05-05
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will comprise patients with colorectal cancer with un-resectable synchronous liver-limited hepatic metastases

Brief summary: This single arm study aims to evaluate the rate of conversion therapy in patients with unresectable liver-limited metastatic colorectal cancer (mCRC) using FOLFOXIRI neoadjuvant regimen and to assess the other outcome including the response rate, the survival rate and the safety profile.

Detailed description: Patients with liver-only metastases colorectal cancer could potentially be cured following surgical resection of metastases. Recent evidence suggest that a triplet chemotherapy regimen, FOLFOXIRI has been associated with higher R0 resection.

Eighty-nine eligible patients will be recruited at Cho Ray hospital in Vietnam. Patients will receive neoadjuvant FOLFOXIRI regimen every two weeks for up to 12 cycles and will undergo periodic imaging studies. The resectability of liver metastases will be assessed by a multidisciplinary team comprised of digestive surgeons, hepato-biliary surgeons, radiologists, and oncologists. This study will be helpful to establish a standard chemotherapy regimen for patients with liver-limited metastatic colorectal cancer. Moreover, this study will assess the surgical outcome, the response rate, the survival rate, the safety of triple drug chemotherapy and the association between conversion operable disease and various survival rate and patient's characteristics.

Eligibility criteria: Inclusion Criteria:

* Patients from 18 to 75 years
* Able to give informed consent
* Have a histological adenocarcinoma diagnosis of colorectal cancer
* Resected or operable colorectal primary tumor
* Initially unresectable liver lesion considered by multidisciplinary team (MDT)
* World Health Organisation performance status (ECOG PS) 0, 1
* Adequate complete blood count, liver and renal function

Exclusion Criteria:

* Prior history of other active malignancies
* Unmeasurable lesion according to RECIST criteria v.1.1
* Recurrence of colorectal cancer
* Resection or ablation of liver lesion
* Distant metastases outside the liver
* Patients who have received prior chemotherapy with Oxaliplatin, Irinotecan, Capecitabine, 5-Fluoro-uracil.
* Concomitant uncontrollable medical status ie. symptomatic cardiac disease, infarction within 24 months, uncontrollable cardiac dysrhythmia, active infectious disease
* Pathology of the liver lesion except adenocarcinoma metastasis from colorectal cancer.

Primary outcomes:
measure: Resectable outcome
timeFrame: 8 weeks
Secondary outcomes:
measure: Progression free survival
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: The incidence of chemotherapy related adverse events
timeFrame: 2 weeks
Other outcomes:
measure: Correlation between R0 procedure and patient's characteristics.
timeFrame: 8 weeks
measure: Correlation between R0 procedure and survival time
timeFrame: 5 years
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Cho Ray hospital- 201 B Nguyen Chi Thanh, District 5
Study officials:
References:
citation: Siriwardena AK, Mason JM, Mullamitha S, Hancock HC, Jegatheeswaran S. Management of colorectal cancer presenting with synchronous liver metastases. Nat Rev Clin Oncol. 2014 Aug;11(8):446-59. doi: 10.1038/nrclinonc.2014.90. Epub 2014 Jun 3.
citation: Masi G, Allegrini G, Cupini S, Marcucci L, Cerri E, Brunetti I, Fontana E, Ricci S, Andreuccetti M, Falcone A. First-line treatment of metastatic colorectal cancer with irinotecan, oxaliplatin and 5-fluorouracil/leucovorin (FOLFOXIRI): results of a phase II study with a simplified biweekly schedule. Ann Oncol. 2004 Dec;15(12):1766-72. doi: 10.1093/annonc/mdh470.
citation: Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis Ch, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D, Georgoulias V. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006 Mar 27;94(6):798-805. doi: 10.1038/sj.bjc.6603011.
citation: Marques RP, Duarte GS, Sterrantino C, Pais HL, Quintela A, Martins AP, Costa J. Triplet (FOLFOXIRI) versus doublet (FOLFOX or FOLFIRI) backbone chemotherapy as first-line treatment of metastatic colorectal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2017 Oct;118:54-62. doi: 10.1016/j.critrevonc.2017.08.006. Epub 2017 Aug 25.