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

Primary Purpose

Rectal Cancer

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
FOLFOXIRI
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal Cancer, Locally advanced rectal cancer, Neoadjuvant, chemotherapy, FOLFOXIRI

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Gastrointestinal Hospital, Sun Yatsen University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFOXIRI

Arm Description

patients received FOLFOXIRI alone for 4 cycles before surgery.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
the local Recurrence rate
the ratio of patients with local recurrence within 3 years
Recurrence free survival
3 years recurrence free survival of this group of patients
Reported Adverse events
Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen.

Full Information

First Posted
August 10, 2014
Last Updated
April 10, 2021
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02217020
Brief Title
Neoadjuvant FOLFOXIRI Chemotherapy Alone for Locally Advanced Rectal Cancer
Acronym
FORTUNE
Official Title
A Phase II Study of Neoadjuvant FOLFOXIRI Chemotherapy Alone in Treating Patients With Locally Advanced Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
August 15, 2014 (undefined)
Primary Completion Date
September 15, 2016 (Actual)
Study Completion Date
August 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Rectal Cancer, Locally advanced rectal cancer, Neoadjuvant, chemotherapy, FOLFOXIRI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FOLFOXIRI
Arm Type
Experimental
Arm Description
patients received FOLFOXIRI alone for 4 cycles before surgery.
Intervention Type
Drug
Intervention Name(s)
FOLFOXIRI
Other Intervention Name(s)
5-FU, Oxaliplatin, Irinotecan
Intervention Description
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
Primary Outcome Measure Information:
Title
The ratio of tumor downstaging to stage 0 and stage I
Description
Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Average neoadjuvant rectal cancer score
Description
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.
Time Frame
2 year
Title
the local Recurrence rate
Description
the ratio of patients with local recurrence within 3 years
Time Frame
3 year
Title
Recurrence free survival
Description
3 years recurrence free survival of this group of patients
Time Frame
3 years
Title
Reported Adverse events
Description
Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Gastrointestinal Hospital, Sun Yatsen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510655
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
35834598
Citation
Zhang J, Li J, Huang M, Xie X, Cai Y, Hu H, Ling J, Wu Z, Deng Y. Neoadjuvant Modified FOLFOXIRI With Selective Radiotherapy in Locally Advanced Rectal Cancer: Long-term Outcomes of Phase II Study and Propensity-Score-Matched Comparison With Chemoradiotherapy. Dis Colon Rectum. 2023 Jul 1;66(7):934-945. doi: 10.1097/DCR.0000000000002424. Epub 2022 Jul 12.
Results Reference
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Neoadjuvant FOLFOXIRI Chemotherapy Alone for Locally Advanced Rectal Cancer

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