Clinical trial NCT02572141: FOLFOX or CAPOX Perioperative Chemotherapy Versus Postoperative Chemotherapy for Locally Advanced Colon Cancer (OPTICAL)
Official title: A Phase III Study to Evaluate the 3-year Disease-free Survival in Patients with Locally Advanced Colon Cancer Receiving Either Perioperative or Postoperative Chemotherapy with FOLFOX or CAPOX Regimens
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colon Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2015-10-08
Enrollment: 738
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 is a robust method for measuring the depth of tumor invasion and identifying the CC patients with poor prognosis, who may benefit from perioperative chemotherapy. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOX or CAPOX regimens compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, locally advanced, but resectable colon cancer.

OBJECTIVE:

The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOX or CAPOX regimens compared to postoperative chemotherapy in patients with locally advanced 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: OVERVIEW OF TRIAL DESIGN:

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

Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Histological or cytological documentation of adenocarcinoma of the colon (≥ 15 cm from the anal verge).
3. 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).
4. Male or female subjects \> 18 years \< 70 of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. CT or MRI scans (done within 30 days of registration) of the chest, abdomen and pelvis all without clear evidence of distant metastatic (M1) disease.
7. Non complicated primary tumor (obstruction, perforation, bleeding).
8. No previous any systemic anticancer therapy for colon cancer disease.
9. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

Exclusion Criteria:

1. Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
2. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
3. Heart failure grade III/IV (NYHA-classification).
4. Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
5. Subjects with known allergy to the study drugs or to any of its excipients.
6. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
7. Breast- feeding or pregnant women
8. Lack of effective contraception.

Primary outcomes:
measure: Disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Curative resection rate
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Relapse-free survival (RFS)
timeFrame: 5 years
measure: Down-staging of primary tumors
timeFrame: 2 years
measure: Toxicity assessed using the NCI common toxicity criteria, version 4.0.
timeFrame: 2 years
measure: Postoperative complications
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sixth Affiliated Hospital, Sun Yat-sen University
name: Yanhong Deng, M.D.
role: PRINCIPAL_INVESTIGATOR
References: