Neoadjuvant FOLFOXIRI Chemotherapy Alone for Locally Advanced Rectal Cancer

Rectal Cancer Clinical Trial

— FORTUNE  

Official title:

A Phase II Study of Neoadjuvant FOLFOXIRI Chemotherapy Alone in Treating Patients With Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02217020
• Other study ID #: GIHSYSU07
• Status: Completed
• Phase: Phase 2
• Start date: August 15, 2014
• Est. completion date: August 15, 2017

Study information

• Verified date: April 2021
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 15, 2017
• Est. primary completion date: September 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• FOLFOXIRI
irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle

Locations

Country	Name	City	State
China	Gastrointestinal Hospital, Sun Yatsen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The ratio of tumor downstaging to stage 0 and stage I	Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I	2 year
Secondary	Average neoadjuvant rectal cancer score	neoadjuvant rectal cancer score (NAR) =[5*pN-3*(cT-pT)+12]^2/9.61 had been proposed and proven to be the surrogate endpoint of overall survival. It refered to the predictive value of lymphnode status and primary tumor downstaging on Overall survival of rectal cancer.	2 year
Secondary	the local Recurrence rate	the ratio of patients with local recurrence within 3 years	3 year
Secondary	Recurrence free survival	3 years recurrence free survival of this group of patients	3 years
Secondary	Reported Adverse events	Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen.	2 years