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

Primary Purpose

Rectal Cancer

Status

Withdrawn

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

FOLFOXIRI

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring neochemotherapy, CRM

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Affiliated Tumor Hospital of Guangxi Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFOXIRI

Arm Description

patients with CRM positive who received FOLFOXIRI alone for 6 cycles before surgery

Outcomes

Primary Outcome Measures

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)

The rate of R0 resection

Evaluation of the resection margin status (positive or negative) in the rectal specimen

Secondary Outcome Measures

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

the local recurrence rate

the rate of patients with local recurrence within 3 years

Recurrence free survival

3 years recurrence free survival of this group of patients

Reported Adverse events

Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen

Full Information

NCT ID

NCT03161574

First Posted

May 18, 2017

Last Updated

August 6, 2019

Sponsor

Guangxi Medical University

1. Study Identification

Unique Protocol Identification Number

NCT03161574

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Withdrawn

Why Stopped

No participants were recruited

Study Start Date

August 11, 2017 (Actual)

Primary Completion Date

December 1, 2019 (Anticipated)

Study Completion Date

June 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Guangxi Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer

Keywords

neochemotherapy, CRM

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FOLFOXIRI

Arm Type

Experimental

Arm Description

patients with CRM positive who received FOLFOXIRI alone for 6 cycles before surgery

Intervention Type

Drug

Intervention Name(s)

FOLFOXIRI

Other Intervention Name(s)

5-Fluorouracil, Oxaliplatin, Irinotecan

Intervention Description

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

Primary Outcome Measure Information:

Title

The rate of negative circumferential margin status

Description

Evaluation of the circumferential margin status (positive or negative) in the rectal specimen according international consensus (positive margin if tumor ≤ 1mm from circumferential margin)

Time Frame

30 days

Title

The rate of R0 resection

Description

Evaluation of the resection margin status (positive or negative) in the rectal specimen

Time Frame

30 days

Secondary Outcome Measure Information:

Title

The rate of tumor downstaging to stage 0 and stage Ⅰ

Description

Tumor downstaging from stage Ⅲ to pathologica complete response （stage 0） and stage Ⅰ

Time Frame

2 years

Title

the local recurrence rate

Description

the rate of patients with local recurrence within 3 years

Time Frame

3 year

Title

Recurrence free survival

Description

3 years recurrence free survival of this group of patients

Time Frame

3 year

Title

Reported Adverse events

Description

Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yuzhou Qin

Organizational Affiliation

Affiated Tumor Hospital of Guangxi Medical University

Official's Role

Study Director

Facility Information:

Facility Name

Affiliated Tumor Hospital of Guangxi Medical University

City

Nanning

State/Province

Guangxi Autonomous Region

ZIP/Postal Code

530021

Country

China

12. IPD Sharing Statement

Plan to Share IPD

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

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