Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

NCT ID: NCT02942563

Last Updated: 2018-01-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-01
• Study Completion Date: 2022-09-30

Brief Summary

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.

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.

Conditions

Rectal Cancer

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

FOLFOXIRI

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Irinotecan; Oxaliplatin; 5-FU; Capecitabine

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ming Ye, Master

Role: PRINCIPAL_INVESTIGATOR

Locations: China, Shanghai Shanghai Jiaotong University School of Medicine, Renji Hospital

Locations

Ethics Committee of Renji Hospital, School of Medicine,Shanghai Jiaotong University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ming Ye, Master

Role: CONTACT

renjiyeming@163.com

+862168383459

Qi Lu, Master

Role: CONTACT

luqi@renji.com

+862158752345 ext. 33364

Facility Contacts

Ming Ye, Master

Role: primary

renjiyeming@163.com

+862168383459

Qi Lu, Master

Role: backup

luqi@renji.com

+862158752345 ext. 33364

Other Identifiers

2016CRC R-001

Identifier Type: -

Identifier Source: org_study_id