Clinical trial NCT03401294: Conversion From Unresectable To Resectable Metastatic Colorectal Cancer.
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic colorectal cancer
Conversion therapy
Liver Metastasectomy
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
First posted: 2018-01-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of liver metastasectomy
timeFrame: Up to 3 years from the date of enrolment into the study
Secondary outcomes:
measure: Response rate
timeFrame: Up to 12 weeks of last cycle of FOLFOXIRI from the date of enrolment till the date of maximum response
measure: 30 days rates of Grade III and IV toxicity
timeFrame: Up to 30 days of last cycle of FOLFOXIRI from the date of enrolment till the date of toxicity
measure: The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
timeFrame: up to 3 years from the date of enrolment or till the progression of the disease
measure: The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer Module (QLQ-CR29)
timeFrame: up to 3 years from the date of enrolment or till the progression of the disease
measure: The European Organization for Research and Treatment of Cancer (EORTC) Colorectal Liver Metastases Module (LMC21)
timeFrame: up to 3 years from the date of enrolment or till the progression of the disease
measure: Early-PET scan response
timeFrame: From the date of enrolment till 8 weeks after four cycles of FOLOXIRI and bevacizumab
measure: Progression-free survival
timeFrame: up to 5 years from the time of enrolment till disease progression or last follow up visit
measure: Overall survival
timeFrame: up to 5 years from the time of enrolment till mortality or last follow up visit
Other outcomes:
Locations:
city: Regina
country: Canada
facility: Allan Balir Cancer Center
state: Saskatchewan
Study officials:
affiliation: University of Saskatchewan
name: Shahid Ahmed, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: