Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02942563
• Other study ID #: 2016CRC R-001
• Status: Recruiting
• Phase: Phase 2
• First received: October 21, 2016
• Last updated: January 1, 2018
• Start date: November 1, 2016
• Est. completion date: September 30, 2022

Study information

• Verified date: December 2017
• Source: RenJi Hospital
• Contact: Ming Ye, Master
• Phone: +862168383459
• Email: renjiyeming[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	Ethics Committee of Renji Hospital, School of Medicine,Shanghai Jiaotong University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

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