Clinical trial NCT05194878: Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers
Official title: Phase III Study of Neoadjuvant FOLFOXIRI Chemotherapy Versus Immediate Surgery for High-risk Resectable Stage II and III Colon Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colon Cancer Stage II
Colon Cancer Stage III
Keywords: neoadjuvent chemotherapy
FOLFOXIRI
colon caner
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-01-18
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: BACKGROUND:

In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography allows a good prediction of tumor stage (wall penetration and nodal involvement) prior to surgery. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOXIRI regimen compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, High-risk, but resectable Stage II or III colon cancer.

OBJECTIVE:

The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOXIRI regimen compared to postoperative chemotherapy in patients with High-risk Resectable Stage II and III colon cancer. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications.

Detailed description: This trial is a a two-arm, multicenter, open labelled, prospective, randomized phase III studies. Eligible patients with High-risk Resectable Stage II and III (T4 or T3 with extramural depth≧5 mm) colon cancer patients will be randomly assigned, in a 2:1 ratio, to receive either perioperative or postoperative chemotherapy.

Eligibility criteria: Inclusion Criteria:

* Histologically proven adenocarcinoma or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer of the colon(≥ 12 cm from the anal verge).
* pMMR in immunohistochemical detection or MSI-H in MSI test.
* Determined preoperatively by either spiral or multidetector CT: high risk T3 (tumor disruption of muscle wall and extension into pericolic fat with more than 5 mm protrusion into adjacent mesenteric fat) or T4 (tumor penetrates to the surface of the visceral peritoneum or directly invades or is adherent to adjacent organs or structures).
* Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
* Adequate full blood count: WBC \>3.0 x109/l; Plts \>100 x109/l. Anaemia (Hb \< 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
* Adequate renal biochemistry: serum creatinine was less than 1.5 times the normal value.
* Adequate hepatobiliary function: serum total bilirubin and ALT were less than 1.5 times the normal value.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

* Any patient for whom radiotherapy is advised by the MDT
* Strong evidence of distant metastases or peritoneal nodules (M1)
* dMMR in immunohistochemical detection or MSI-L/MS-S in MSI test.
* Peritonitis (secondary to perforated tumour)
* Colonic obstruction that has not been defunctioned
* Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (\<6 months) MI
* Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
* Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk \<5%

Primary outcomes:
measure: Disease-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Down-staging of primary tumors
timeFrame: 1 year
measure: Chemotherapy toxicity
timeFrame: through chemotherapy administration, up to 6 months
measure: R0 resection rate
timeFrame: after surgery completed, up to 1 month
measure: Surgical morbidity
timeFrame: 30 days post surgery
measure: CT staging
timeFrame: from randomization to surgery completed, up to 6 months
measure: CT assessment of response to neoadjuvant treatment
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: 651 Dongfeng Road East
state: Guangdong
Study officials:
References: