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

NCT ID: NCT03161574

Last Updated: 2019-08-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-11
• Study Completion Date: 2022-06-01

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.

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOXIRI

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

Group Type: EXPERIMENTAL

FOLFOXIRI

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

5-Fluorouracil; Oxaliplatin; Irinotecan

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangxi Medical University

OTHER

Sponsor Role: lead

Responsible Party

Wu Liucheng

Attending Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuzhou Qin

Role: STUDY_DIRECTOR

Affiated Tumor Hospital of Guangxi Medical University

Locations

Affiliated Tumor Hospital of Guangxi Medical University

Nanning, Guangxi Autonomous Region, China

Countries

China

Other Identifiers

FOLOXIRIREC

Identifier Type: -

Identifier Source: org_study_id