Conversion From Unresectable To Resectable Metastatic Colorectal Cancer. (CONVERSION)
Primary Purpose
Metastatic Colorectal Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
FOLFOXIRI and Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic colorectal cancer, Conversion therapy, Liver Metastasectomy
Eligibility Criteria
Inclusion Criteria:
- Adult patients, aged between 18 and 70 years with histologically proven adenocarcinoma or poorly differentiated carcinoma of the colon and rectum with unresectable liver-only metastases and no extra-hepatic disease.
- World Health Organization (WHO) performance status of 0-1.
- No previous chemotherapy for advanced disease.
- Adequate functioning of the bone marrow, liver, and kidneys.
Exclusion Criteria:
- Breastfeeding or pregnancy.
- An active second primary cancer with the exception of squamous cell carcinoma of the skin or an in situ cancer.
- Severe or uncompensated concomitant medical conditions.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Single arm
Arm Description
FOLFOXIRI and Bevacizumab
Outcomes
Primary Outcome Measures
Rate of liver metastasectomy
Conversion From Unresectable To Resectable Liver Metastases
Secondary Outcome Measures
Response rate
Based on RECIST criteria
30 days rates of Grade III and IV toxicity
As per National Cancer Institute Common Toxicity Criteria
The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Quality of life questionnaire related to cancer and its treatment
The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer Module (QLQ-CR29)
Quality of life questionnaire specifically related to colorectal cancer
The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Liver Metastases Module (LMC21)
Quality of life questionnaire specifically related to liver metastases
Early-PET scan response
change in FDG-uptake between baseline and after 4 cycles of chemotherapy and it correlation with rate of metastasectomy
Progression-free survival
progression following FOLOXIRI and bevacizumab
Overall survival
all cause mortality
Full Information
NCT ID
NCT03401294
First Posted
January 2, 2018
Last Updated
October 31, 2022
Sponsor
University of Saskatchewan
1. Study Identification
Unique Protocol Identification Number
NCT03401294
Brief Title
Conversion From Unresectable To Resectable Metastatic Colorectal Cancer.
Acronym
CONVERSION
Official Title
Conversion From Unresectable To Resectable Liver Metastases In Patients With Liver-Only Metastatic Colorectal Cancer Treated With FOLFOXIRI Plus Bevacizumab. The Conversion Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2023 (Anticipated)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Saskatchewan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Most patients with mCRC are treated with palliative chemotherapy and only a small number of patients with limited metastatic disease achieve long-term remission following metastasectomy. There is a growing need for more effective treatment in patients with liver-only mCRC to improve the rate of curative resection without compromising QOL.The current study is informed by our patient's needs. It aims to evaluate the rate of conversion therapy in patients with unresectable liver-only mCRC using the combination of FOLFOXIRI and bevacizumab and to assess the association between an early FDG-PT/CT response and other clinical and pathological biomarkers and hepatic metastasectomy.
Detailed Description
Colorectal cancer is the second leading cause of cancer-related death in North America. Patients with metastatic colorectal cancer generally have limited life expectancy, however, a small number of patients with liver-only metastases could potentially be cured following surgical resection of metastases. Patients and their family strongly feel that there is an unmet need for a more effective treatment in metastatic colorectal cancer to improve disease response rate and thereby curative surgery. Recent evidence suggest that a triplet chemotherapy regimen, FOLFOXIRI plus bevacizumab has been associated with higher response rates. The CONVERSION trial will evaluate the rate of conversion from unresectable to resectable liver metastases in patients with liver-only metastatic colorectal cancer treated with FOLFOXIRI-bevacizumab. Furthermore, this study will assess disease control rate, survival, quality of life and association between various biomarkers including an early FDG-PET/CT response and curative surgery. Thirty-two eligible patients will be recruited at the two major cancer centers in Saskatchewan. Patients will receive FOLFOXIRI-bevacizumab every two weeks for a total of 12 cycles and will undergo periodic imaging studies. The resectability of liver metastases will be assessed by a multidisciplinary team comprised of surgeons, radiologists, and oncologists. This study will be helpful to establish a standard chemotherapy regimen for patients with liver-only metastatic colorectal cancer and to determine the role of FDG-PET/CT scan and other biomarkers in predicting curative surgery. Complete resection of metastases will allow such patients to discontinue chemotherapy and live a normal life.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic colorectal cancer, Conversion therapy, Liver Metastasectomy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Other
Arm Description
FOLFOXIRI and Bevacizumab
Intervention Type
Drug
Intervention Name(s)
FOLFOXIRI and Bevacizumab
Other Intervention Name(s)
5FU, leucovorin, oxaliplatin, irinotecan and bevacizumab
Intervention Description
Every 2 week for a total of 12 cycles
Primary Outcome Measure Information:
Title
Rate of liver metastasectomy
Description
Conversion From Unresectable To Resectable Liver Metastases
Time Frame
Up to 3 years from the date of enrolment into the study
Secondary Outcome Measure Information:
Title
Response rate
Description
Based on RECIST criteria
Time Frame
Up to 12 weeks of last cycle of FOLFOXIRI from the date of enrolment till the date of maximum response
Title
30 days rates of Grade III and IV toxicity
Description
As per National Cancer Institute Common Toxicity Criteria
Time Frame
Up to 30 days of last cycle of FOLFOXIRI from the date of enrolment till the date of toxicity
Title
The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Description
Quality of life questionnaire related to cancer and its treatment
Time Frame
up to 3 years from the date of enrolment or till the progression of the disease
Title
The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer Module (QLQ-CR29)
Description
Quality of life questionnaire specifically related to colorectal cancer
Time Frame
up to 3 years from the date of enrolment or till the progression of the disease
Title
The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Liver Metastases Module (LMC21)
Description
Quality of life questionnaire specifically related to liver metastases
Time Frame
up to 3 years from the date of enrolment or till the progression of the disease
Title
Early-PET scan response
Description
change in FDG-uptake between baseline and after 4 cycles of chemotherapy and it correlation with rate of metastasectomy
Time Frame
From the date of enrolment till 8 weeks after four cycles of FOLOXIRI and bevacizumab
Title
Progression-free survival
Description
progression following FOLOXIRI and bevacizumab
Time Frame
up to 5 years from the time of enrolment till disease progression or last follow up visit
Title
Overall survival
Description
all cause mortality
Time Frame
up to 5 years from the time of enrolment till mortality or last follow up visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients, aged between 18 and 70 years with histologically proven adenocarcinoma or poorly differentiated carcinoma of the colon and rectum with unresectable liver-only metastases and no extra-hepatic disease.
World Health Organization (WHO) performance status of 0-1.
No previous chemotherapy for advanced disease.
Adequate functioning of the bone marrow, liver, and kidneys.
Exclusion Criteria:
Breastfeeding or pregnancy.
An active second primary cancer with the exception of squamous cell carcinoma of the skin or an in situ cancer.
Severe or uncompensated concomitant medical conditions.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shahid Ahmed, MD, PhD
Phone
3066552710
Email
shahid.ahmed@saskcancer.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Moser
Phone
(306) 966-8641
Email
michael.moser@usask.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shahid Ahmed, MD, PhD
Organizational Affiliation
University of Saskatchewan
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Conversion From Unresectable To Resectable Metastatic Colorectal Cancer.
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