FOLFOXIRI Chemotherapy Alone as Neoadjuvant Treatment for Circumferential Radial Margin (CRM) Positive Rectal Cancer

Sponsor

Guangxi Medical University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03161574

Collaborator

(none)

Enrollment

Location

Arm

57.7

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Neoadjuvant 5-Fu based chemoradiation followed by surgery is a standard treatment for locally advanced rectal cancer. However, radiation-related side effects could not be neglected. But this multimodality strategy failed to improve survival. Neoadjuvant chemotherapy alone may be an alternative strategy to minimize treatment-related toxicities without compromising the oncology outcome. Thus, patients with MRI-defined CRM-positive rectal cancer will receive 6 cycles of neoadjuvant treatment with FOLFOXIRI followed by surgery. The purpose of the study is to evaluate the efficacy of FOLFOXIRI alone as neoadjuvant treatment in treating patients with locally advanced rectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: FOLFOXIRI	Phase 2

Detailed Description

Preoperative chemoradiotherapy has been considered for years the standard treatment to patients with locally advanced rectal cancer. However, this multi-modality treatment has been questioned since more evidences suggested that radiotherapy may not be a necessary component of this treatment, and by omitting radiotherapy it have the advantage of reducing acute and late treatment-related toxicities. Given the high anti-tumor of systemic chemotherapy alone, any patients with CRM involvement could be theoretically deemed candidate for an approach in which radiotherapy is delivered preoperatively if a substantial tumor downsizing is not achieved after upfront systemic chemotherapy or postoperatively if the pathologic CRM is involved. This single phase Ⅱ trial was aimed to evaluate the efficacy of FOLFOXIRI in treating patients with MRI-defined CRM-positive rectal cancer. All patients will receive the regimen every 2 weeks for 3 cycles. MRI of the pelvic will be performed after 3 cycles of chemotherapy to assess clinical response. If the tumor responds after 3 cycles of treatment, the patient will continue for another 3 cycles of treatment before surgery under the decision of MDT. On the contrary, if the tumor shows no response, radiotherapy will be given before operation. After surgery and pathologic CRM is not involved, 6 cycles of mFOLFOX6 will be given as adjuvant chemotherapy, otherwise postoperative radiotherapy will be given if the pathologic CRM is involved.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

FOLFOXIRI Chemotherapy Alone as Neoadjuvant Treatment for MRI-defined Circumferential Radial Margin (CRM) Positive Rectal Cancer

Actual Study Start Date :

Aug 11, 2017

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FOLFOXIRI patients with CRM positive who received FOLFOXIRI alone for 6 cycles before surgery	Drug: FOLFOXIRI irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle Other Names: 5-Fluorouracil Oxaliplatin Irinotecan

Arm

Intervention/Treatment

Experimental: FOLFOXIRI

patients with CRM positive who received FOLFOXIRI alone for 6 cycles before surgery

Drug: FOLFOXIRI

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

Other Names:

5-Fluorouracil

Oxaliplatin

Irinotecan

Outcome Measures

Primary Outcome Measures

The rate of negative circumferential margin status [30 days]
Evaluation of the circumferential margin status (positive or negative) in the rectal specimen according international consensus (positive margin if tumor ≤ 1mm from circumferential margin)
The rate of R0 resection [30 days]
Evaluation of the resection margin status (positive or negative) in the rectal specimen

Secondary Outcome Measures

The rate of tumor downstaging to stage 0 and stage Ⅰ [2 years]
Tumor downstaging from stage Ⅲ to pathologica complete response （stage 0） and stage Ⅰ
the local recurrence rate [3 year]
the rate of patients with local recurrence within 3 years
Recurrence free survival [3 year]
3 years recurrence free survival of this group of patients
Reported Adverse events [3 years]
Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of adenocarcinoma of the rectum
Age: 18-70years old
Signed informed consent; able to comply with study and/or followup procedures
Stage of the primary tumor may be determined by MRI as CRM positive
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.
No renal disease that would preclude study treatment or followup
ECOG status: 0～1

Exclusion Criteria:

Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
Less than 4 weeks since prior participation in any investigational drug study
History of invasive rectal malignancy, regardless of disease free interval
Uncontrolled hypertension
Cardiovascular disease that would preclude study treatment or followup
Lack of upper gastrointestinal tract integrity or malabsorption syndrome，active upper gastrointestinal tract bleeding
Synchronous colon cancer
Pregnant or nursing
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.