Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

The concurrent neoadjuvant chemoradiation therapy is standard care for local advanced rectal cancer (LARC), however, this regimen may induce sorts of adverse events, and part of them even more severer. A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone, but the results did not increase the ratio of pathological complete response (pCR), which was associated with overall survival (OS). Here, the investigators adopt the three active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) as the neoadjuvant chemotherapy regimen to replace the concurrent chemoradiation and to improve the ratio of pCR further.

Study Overview

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

Detailed Description

This is a multicenter, phase II trial to assess the efficacy/safety of triplet regimen (FOLFOXIRI) for patients with LARC. After 4 cycles of FOLFOXIRI and 2 weeks later, the patients will be evaluated by senior radiologist, oncologist and surgeon through pelvic MRI, CT and Positron Emission Computed Tomography (PET-CT). The patients will go to surgery (TME) if the tumor response is good enough to have complete resection under the decision of MDT,otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/M^2, bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Ethics Committee of Renji Hospital, School of Medicine,Shanghai Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 to 75 years at diagnosis
• Diagnosis of rectal adenocarcinoma
• ECOG status: 0～1
• Clinical stage II (T3-4, N0) or stage III (T1-4, N1-2)
• Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
• Leukocytes ≥ 4.0 x109/ L,
• Absolute neutrophil count (ANC) ≥ 2.0 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) ≤ 3 x ULN
• Aspartate aminotransferase (AST) ≤ 3 x ULN.
• Serum creatinine ≤ 1.5 x the ULN.
• Signed informed consent;

Exclusion Criteria:

• Patient had received pelvic radiotherapy
• Patient had received systemic chemotherapy
• Pregnant and Nursing women
• Had metastatic disease
• Uncontrolled co-morbid illnesses or other concurrent disease
• Patient had second malignant disease within 5 years
• 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; 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

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 for 4-6 cycles, Chemoradiation for patients who are not suitable to surgery: Pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/m², bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.; Other Names: 5-FU; Capecitabine; Irinotecan; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pelvic complete resection rate	Pathologic confirmation	Up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of local control	Imaging diagnosis	3 years
Disease free survival (DFS)	Imaging diagnosis	3 years
Overall survival	Record document	3 years
The rate of receive chemoradiation	Record document	Up to 10 weeks
The rate of clinical complete response after 4 cycles of FOLFOXIRI	Imaging diagnosis	Up to 10 weeks
The rate of pathological complete response after 4 cycles of FOLFOXIRI	Pathologic confirmation	Up to 10 weeks
The incidence of >=3 grade adverse events	Common Terminology Criteria for Adverse Events v3.0 (CTCAE)	2 years

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Ming Ye, Master, Locations: China, Shanghai Shanghai Jiaotong University School of Medicine, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Anticipated): September 30, 2019
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): January 3, 2018
• Last Update Submitted That Met QC Criteria: January 1, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: FOLFOXIRI; Local Advanced Rectal Cancer; Total Neoadjuvant Therapy
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Oxaliplatin; Irinotecan
• Other Study ID Numbers: 2016CRC R-001