Clinical trial NCT02167321: Rectal Cancer, Adjuvant Chemotherapy, FOLFOX(5-fluorouracil/Leucovorin/Oxaliplatin), Total Mesorectal Excision
Official title: Adjuvant Chemotherapy With FOLFOX After Total Mesorectal Excision for Locally Advanced Rectal Cancer; an Open-label, Multicenter, Prospective, Randomized Phase 3 Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2014-06-19
Enrollment: 90
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The introduction of total mesorectal excision (TME) and the progress of neoadjuvant chemoradiotherapy has significantly reduced the risk of local recurrence in locally advanced rectal cancer. However, systemic recurrence rate is not being improved and that is considered as the cause of unsatisfactory overall survival of patients with rectal cancer. Relatively higher systemic relapse rate than local recurrence rate is probably due to the insufficient control of systemic micrometastasis during adjuvant chemotherapy. The efficacy of adjuvant combination cytotoxic chemotherapy after surgery in treatment of rectal cancer remains controversial. In addition, preoperative radiotherapy increases surgical complication such as anastomosis site leakage and radiotherapy itself worsen sexual and urinary function and bowel habit which result in aggravation of the quality of life. Furthermore the preoperative chemoradiotherapy upto 3 months not only extends treatment period but increases cost of care. To reduce the possibility of overtreatment, it is needed to confirm that the preoperative chemoradiotherapy is absolutely necessary to locally advanced rectal cancer patients with safe circumferential margin (CRM) resected curatively by standardized TME operation.

In this study, investigators aim to evaluate the efficacy of adjuvant FOLFOX chemotherapy after TME without preoperative chemoradiotherapy in patients with locally advanced rectal cancer having spared CRM are not inferior to that of current standard treatment.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the rectum below 10 cm from the anal verge
2. Locally advanced rectal cancer (T3N0 or T1-3N+)
3. Age: 19-80 years old.
4. Without evidence of distant metastasis including paraortic lymph node, common \& external iliac lymph node metastasis
5. MRI scan confirmed more than 2 mm circumferential margin
6. ECOG(Eastern Cooperative Oncology Group) performance status 0-2
7. preoperative ASA class I-III
8. No prior systemic treatment for rectal cancer (i.e. chemotherapy or immunotherapy)
9. No history of regional radiation treatment in the pelvic cavity
10. Adequate hematologic function: ANC(absolute neutrophil count) ≥ 1.5×109/L，Platelet ≥ 100×109/L, Adequate renal function: Cr ≤ 1.5×ULN or Glomerular filtration rate (Ccr calculated by Cockcroft formula) ≥ 50 ml/min, Adequate hepatic function: ALT(Alanine aminotransferase)/AST(aspartate aminotransferase) ≤ 2.5×ULN, Total bilirubin ≤ 1.5×ULN
11. Patients must be willing and able to comply with the protocol duration of the study
12. Signed informed consent

Exclusion Criteria:

1. Malignancy of the rectum other than adenocarcinoma or adenocarcinoma developed from inflammatory bowel disease
2. Suspicious distant metastasis
3. Patients with peripheral neuropathy ≥ NCI CTC(common terminology criteria) grade 1
4. Uncontrolled and significant cardiovascular disease (i.e. NYHA(New York Heart Association) class III or IV heart failure, myocardial infarction within the past 6 months, uncontrolled angina pectoris)
5. Uncontrolled active infection or serious concomitant systemic disorders incompatible with the study
6. Other co-existing malignancy or malignancy within the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin
7. Patients requiring immunosuppressive treatment who received organ transplantation
8. Uncontrolled epilepsy and psychiatric disease
9. Pregnant or lactating patient
10. Females with a positive or no pregnancy test unless childbearing potential can be otherwise excluded (amenorrheic for at least 2 years,hysterectomy or oophorectomy)
11. Patients receiving a concomitant treatment with drugs interacting with 5-Fluorouracil or oxaliplatin such as flucytosine, phenytoin, or warfarin
12. Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-Fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.
13. Known hypersensitivity to platinum-based drugs, leucovorin or capecitabine
14. Patients taking sorivudine or brivudine
15. Patients taking tegafur, gimeracil, oteracil potassium complex or stopped the medication within 7days before.
16. Patients who have hereditary disease like as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, etc.
17. Participant in any clinical trial within 4 weeks before initiation of the study
18. Treatment with bevacizumab, cetuximab, oxaliplatin or irinotecan before screening

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: 3 years
Secondary outcomes:
measure: Disease free survival (DFS)
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 3 years and 5 years
measure: Local recurrence rate
timeFrame: 3 years and 5 years
measure: Systemic recurrence rate
timeFrame: 3 years and 5 years
measure: Total score for function of urination (IPSS) and defecation (Wexner's score)
timeFrame: 1 month and 6 months after surgery
measure: Evaluation for rate of various events after surgery
timeFrame: 14 days after surgery
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
References:
citation: Lee JB, Kim HS, Jung I, Shin SJ, Beom SH, Chang JS, Koom WS, Kim TI, Hur H, Min BS, Kim NK, Park S, Jeong SY, Baek JH, Kim SH, Lim JS, Lee KY, Ahn JB. Upfront radical surgery with total mesorectal excision followed by adjuvant FOLFOX chemotherapy for locally advanced rectal cancer (TME-FOLFOX): an open-label, multicenter, phase II randomized controlled trial. Trials. 2020 Apr 7;21(1):320. doi: 10.1186/s13063-020-04266-6.