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Totally Neoadjuvant FOLFOXIRI + Short-course Radiation + XELOX in Patients With Locally Advanced Rectal Cancer

Primary Purpose

Rectal Neoplasms, Drug Therapy, Radiation

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
FOLFOXIRI
Short-Course Radiation Therapy(5Gy*5)
XELOX
Sponsored by
China Medical University, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Neoplasms

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age: 18-75 years old
  • Primary and pathological diagnosis of rectal adenocarcinoma
  • Radiographic evaluation of initial resectable rectal cancer
  • T staging was determined by MRI as T3N+ or T4Nx
  • Distal border of the tumor must be located < 12 cm from the anal verge
  • ECOG status: 0～1
  • Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

Neutrophil count≥1.5×10^9/L Platelet count≥90×10^9/L Hemoglobin≥90g/L Total bilirubin (TBI) ≤ 1.5 * ULN Alanine aminotransferase (ALT)≤2.5 * ULN Aspartate aminotransferase (AST)≤2.5 * ULN Alkaline phosphatase (ALP)≤2.5 * ULN

- Signed informed consent; able to comply with study and/or follow- up procedures

Exclusion Criteria:

  • Previous treatment with oxaliplatin, irinotecan or fluorouracil
  • Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
  • Clear indication of involvement of the pelvic side walls by imaging
  • With distant metastasis
  • A history of malignant rectal cancer (i. e. sarcoma, lymphoma, carcinoid, squamous cell carcinoma) or synchronous colon cancer
  • Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; active ischemic heart disease; myocardial infarction within the past 6 months; symptomatic arrhythmia uncontrolled hypertension. Unexplained syncope occurred within 3 months
  • Digestive system diseases that would preclude study treatment or follow-up within the past 6 months
  • Gastric ulcers or duodenal ulcers for the treatment of resistance;
  • 3 or 4 grade gastrointestinal bleeding / bleeding;
  • Gastrointestinal perforation / fistula;
  • Abdominal abscess;
  • Infectious or inflammatory bowel disease
  • HIV infection and/or active hepatitis B virus infection
  • Pregnant or lactating women. Fertile patients must use effective contraception
  • Any serious acute or chronic disease that can not be involved in the study or to influence the interpretation of the results of the study
  • Other intervention clinical trials were combined at the same time.
  • Nerve or mental abnormality affecting cognitive ability
  • Other malignancy except effectively treated squamous cell or basal cell skin cancer,
  • Other situations that the researchers think should be excluded

Sites / Locations

  • China Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFOXIRI+short-course radiation+XELOX

Arm Description

Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by surgery.

Outcomes

Primary Outcome Measures

The ratio of tumor downstaging to stage 0 and stage I
Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I

Secondary Outcome Measures

Tumor regression grade (TRG)
The level of tumor regression under pathological examination
Disease free survival
Estimated from the date of surgery to the date of recurrence.
Overall survival time
Estimated from the date of enrollment to death from any cause.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The grade of toxicity will be assessed using the NCI-CTCAE version 4.0.
ctDNA change
The relationship between ctDNA and survival will be evaluated.
SUVmax changes
Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy
Quality of life (QLQ C30)
Scores according to EORTC QLQ-C30 scoring manual

Full Information

First Posted
March 23, 2018
Last Updated
April 13, 2021
Sponsor
China Medical University, China
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1. Study Identification

Unique Protocol Identification Number
NCT03484221
Brief Title
Totally Neoadjuvant FOLFOXIRI + Short-course Radiation + XELOX in Patients With Locally Advanced Rectal Cancer
Official Title
Totally Neoadjuvant FOLFOXIRI Chemotherapy Followed by Short-course Radiation and XELOX Chemotherapy in Patients With Locally Advanced Rectal Cancer：an Open-label, Single-arm, Multicenter Phase II Study.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 1, 2018 (Actual)
Primary Completion Date
October 1, 2021 (Anticipated)
Study Completion Date
April 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
China Medical University, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
To evaluate the efficacy and safety of totally neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) followed by short-course radiation therapy and XELOX chemotherapy in the patients with locally advanced rectal cancer.
Detailed Description
Neoadjuvant chemoradiation therapy with double cytotoxic agents is the standard treatment for the patients with locally advanced rectal cancer. Conventional treatment reduced the local recurrence but did not prolong the long-term survival. Furthermore, the patients with pathological complete response (pCR) did not benefit from double cytotoxic chemotherapy. Therefore, we chose triple cytotoxic agents FOLFOXIRI as the neoadjuvant chemotherapy. We will evaluate the efficacy and safety of totally neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) followed by short-course radiation and XELOX chemotherapy in the patients with locally advanced rectal cancer to achieve more pCR and longer survival. In this prospective study, 30 patients with locally advanced rectal cancer will be recruited. Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by TME surgery. PET-CT examination will be performed before and after the 4 cycles of neoadjuvant FOLFOXIRI chemotherapy to assess the SUVmax changes. In addition, the dynamic changes of ctDNA in peripheral blood will be monitored at the PET-CT examination. In the course of treatment, safety evaluation will be carried out according to the standard of adverse reaction classification (CTCAE) 4.0.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Neoplasms, Drug Therapy, Radiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FOLFOXIRI+short-course radiation+XELOX
Arm Type
Experimental
Arm Description
Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by surgery.
Intervention Type
Drug
Intervention Name(s)
FOLFOXIRI
Other Intervention Name(s)
Irinotecan, Oxaliplatin, 5-Fluorouracil
Intervention Description
IRINOTECAN 150 mg/m^2 IV over 1-h, day 1 + OXALIPLATIN 85 mg/m^2 IV over 2-h, day 1 + L-LEUCOVORIN 200 mg/m^2 IV over 2-h, day 1 + 5-FLUOROURACIL 2800 mg/m^2 IV 48-h continuous infusion, starting on day 1 administered every two weeks for 4 cycles (2 months).
Intervention Type
Radiation
Intervention Name(s)
Short-Course Radiation Therapy(5Gy*5)
Intervention Description
Patients received a short-course radiation therapy(5Gy*5) after 4 cycles of FOLFOXIRI.
Intervention Type
Drug
Intervention Name(s)
XELOX
Other Intervention Name(s)
Capecitabine, Oxaliplatin
Intervention Description
OXALIPLATIN 130 mg/m^2 IV over 2-h, day 1 Capecitabine 1000 mg/m^2 twice daily days 1-14 every 3 weeks for 4 cycles.
Primary Outcome Measure Information:
Title
The ratio of tumor downstaging to stage 0 and stage I
Description
Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Tumor regression grade (TRG)
Description
The level of tumor regression under pathological examination
Time Frame
2 years
Title
Disease free survival
Description
Estimated from the date of surgery to the date of recurrence.
Time Frame
3 years
Title
Overall survival time
Description
Estimated from the date of enrollment to death from any cause.
Time Frame
3 years
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
The grade of toxicity will be assessed using the NCI-CTCAE version 4.0.
Time Frame
3 years
Title
ctDNA change
Description
The relationship between ctDNA and survival will be evaluated.
Time Frame
3 years
Title
SUVmax changes
Description
Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy
Time Frame
At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days)
Title
Quality of life (QLQ C30)
Description
Scores according to EORTC QLQ-C30 scoring manual
Time Frame
Every 2 weeks after the first treatment until 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18-75 years old Primary and pathological diagnosis of rectal adenocarcinoma Radiographic evaluation of initial resectable rectal cancer T staging was determined by MRI as T3N+ or T4Nx Distal border of the tumor must be located < 12 cm from the anal verge ECOG status: 0～1 Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Neutrophil count≥1.5×10^9/L Platelet count≥90×10^9/L Hemoglobin≥90g/L Total bilirubin (TBI) ≤ 1.5 * ULN Alanine aminotransferase (ALT)≤2.5 * ULN Aspartate aminotransferase (AST)≤2.5 * ULN Alkaline phosphatase (ALP)≤2.5 * ULN - Signed informed consent; able to comply with study and/or follow- up procedures Exclusion Criteria: Previous treatment with oxaliplatin, irinotecan or fluorouracil Hypersensitivity to fluorouracil, oxaliplatin or irinotecan. Clear indication of involvement of the pelvic side walls by imaging With distant metastasis A history of malignant rectal cancer (i. e. sarcoma, lymphoma, carcinoid, squamous cell carcinoma) or synchronous colon cancer Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; active ischemic heart disease; myocardial infarction within the past 6 months; symptomatic arrhythmia uncontrolled hypertension. Unexplained syncope occurred within 3 months Digestive system diseases that would preclude study treatment or follow-up within the past 6 months Gastric ulcers or duodenal ulcers for the treatment of resistance; 3 or 4 grade gastrointestinal bleeding / bleeding; Gastrointestinal perforation / fistula; Abdominal abscess; Infectious or inflammatory bowel disease HIV infection and/or active hepatitis B virus infection Pregnant or lactating women. Fertile patients must use effective contraception Any serious acute or chronic disease that can not be involved in the study or to influence the interpretation of the results of the study Other intervention clinical trials were combined at the same time. Nerve or mental abnormality affecting cognitive ability Other malignancy except effectively treated squamous cell or basal cell skin cancer, Other situations that the researchers think should be excluded
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuanhe Wang, PhD
Phone
18900918794
Email
zhangjd0228@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jingdong Zhang
Organizational Affiliation
China Medical University, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
China Medical University
City
Shenyang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuanhe Wang

12. IPD Sharing Statement

Learn more about this trial

Totally Neoadjuvant FOLFOXIRI + Short-course Radiation + XELOX in Patients With Locally Advanced Rectal Cancer

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