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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: FOLFOXIRI

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangxi Autonomous Region
    • Nanning, Guangxi Autonomous Region, China, 530021
      • Affiliated Tumor Hospital of Guangxi Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Irinotecan; 5-Fluorouracil; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Guangxi Medical University
• Investigators: Study Director: Yuzhou Qin, Affiated Tumor Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 18, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): August 8, 2019
• Last Update Submitted That Met QC Criteria: August 6, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: CRM; neochemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Oxaliplatin; Irinotecan
• Other Study ID Numbers: FOLOXIRIREC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No