Neoadjuvant FOLFOXIRI Chemotherapy Alone for Locally Advanced Rectal Cancer (FORTUNE)

Sun Yat-sen University

Status and phase

Completed

Phase 2

Conditions

Rectal Cancer

Treatments

Drug: FOLFOXIRI

Study type

Interventional

Funder types

Other

Identifiers

NCT02217020

GIHSYSU07

Details and patient eligibility

About

The standard treatment for stage 2/3 rectal cancer is neoadjuvant 5-Fu based chemoradiation. However, preoperative radiation cause kinds of adverse events, some were irreversible. And the survival benefit was not obvious. Whether chemotherapy alone is effective enough in treating rectal cancer is not yet known. Here, the investigators chose all the three active cytotoxic agents (5-FU, Oxaliplatin, Irinotecan) as the neoadjuvant treatment regimen (FOLFOXIRI). The purpose of the study is to evaluate the efficacy of FOLFOXIRI as neoadjuvant regimen in treating patients with locally advanced rectal cancer.

Full description

Preoperative chemoradiotherapy could improve the local control of locally advanced rectal cancer, but the role was limited, only 5%. The adverse event cause by radiotherapy was severe. This single phase II trial was aimed to evaluate the efficacy of triplet regimen (FOLFOXIRI) in treating patients with locally advanced rectal cancer. All patients will receive the study regimen every 2 weeks for 4-6 cycles. MRI of the pelvic will be performed after 4 cycles of chemotherapy to assess clinical response. If the tumor response over 20% after 4 cycles of treatment, the patient will go to surgery (TME) directly or 2 more cycles of treatment before surgery under the decision of MDT. On the contrary, if the tumor show poor response (<20%), radiotherapy will be performed before operation. After surgery, 6-8 cycles of mFOLFOX6 will be given as adjuvant chemotherapy.

Enrollment

100 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Diagnosis of adenocarcinoma of the rectum
Age: 18-70 years old
Signed informed consent; able to comply with study and/or follow- up procedures
Stage of the primary tumor may be determined by ultrasound or MRI
Stage II (T3-4, N0 [N0 is defined as all imaged lymph nodes < 1.0 cm]) OR stage III (T1-4, N1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]
Tumor palpable by digital rectal exam OR accessible by proctoscope or sigmoidoscope
Distal border of the tumor must be located < 12 cm from the anal verge
Tumor amenable to curative resection
Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥ 9g/ dL.
Total bilirubin ≤1.5 x the upper limit of normal (ULN).
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
Alkaline phosphatase limit ≤ 5x ULN.
Amylase and lipase ≤ 1.5 x the ULN.
Serum creatinine ≤ 1.5 x the ULN.
Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.
No renal disease that would preclude study treatment or follow-up
ECOG status: 0～1

Exclusion Criteria:

Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
No More than 4 weeks since prior participation in any investigational drug study
More than 4 weeks since prior participation in any investigational drug study
Clear indication of involvement of the pelvic side walls by imaging
With distant metastasis
History of invasive rectal malignancy, regardless of disease-free interval
Fertile patients must use effective contraception
Uncontrolled hypertension
Cardiovascular disease that would preclude study treatment or follow-up
Lack of upper gastrointestinal tract integrity or malabsorption syndrome，active upper gastrointestinal tract bleeding
Synchronous colon cancer
Pregnant or nursing, Fertile patients do not use effective contraception
Other malignancy within the past 5 years except effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum
No psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation
patients refused to signed informed consent.