Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic colorectal cancer, Phase III, FOLFOXIRI, FOLFIRI
Brief summary
The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of response rate to conventional chemotherapy with the FOLFIRI regimen as first-line treatment of metastatic colorectal cancer patients.
Detailed description
Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs in the course of the disease, but not with the proportion of patients who receive any second-line therapy. In a sequential strategy, not all patients who progress after first-line chemotherapy are able to receive second-line treatment. Moreover, there is a correlation between the response rate to chemotherapy and the postchemotherapy radical resection rate of metastases. Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a first-line regimen containing the three active agents.
Interventions
DRUGFOLFIRI
Irinotecan 180 mg/sqm on day 1 Leucovorin 100 mg/sqm on day 1 and day 2 5-fluorouracil 400 mg/sqm bolus followed by 5-fluorouracil 600 mg/sqm 22-hour continuous infusion on day 1 and day 2 Repeated every 2 weeks
DRUGFOLFOXIRI
Irinotecan 165 mg/sqm on day 1 Oxaliplatin 85 mg/sqm on day 1 Leucovorin 200 mg/sqm on day 1 5-fluorouracil 3200 mg/sqm 48-hour continuous infusion starting on day 1 Repeated every 2 weeks
Sponsors
Gruppo Oncologico del Nord-Ovest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* adenocarcinoma of the colon or rectum * unresectable metastatic disease * age 18 to 75 years * Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower if age 70 years or younger or ECOG performance status of 0 if age 71 to 75 years measurable disease according to WHOcriteria * leukocyte count of at least 3,500/mm3, neutrophils count of at least 1,500/mm3, platelet count of at least 100,000/mm3 * serum creatinine of 1.3 mg/dL or less * serum bilirubin less than 1.5 mg/dL and AST, ALT, and alkaline phosphatase 2.5 x normal values or less (\</= 5 if liver metastases) * previous fluoropyrimidine-based adjuvant chemotherapy was allowed if ended more than 6 months before random assignment
Exclusion criteria
* previous palliative chemotherapy for metastatic disease * previous chemotherapy including irinotecan or oxaliplatin * symptomatic cardiac disease, myocardial infarction in the last 24 months or uncontrolled arrhythmia * active infections * inflammatory bowel disease * total colectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate (RR) | Responses are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of treatment (6 months) | Responses are evaluated every 8 weeks according to WHO criteria. The determination of responses and progression was initially based on investigator-reported measurements; computed tomography scans of all responding patients and of patients with stable disease were subsequently subjected to external review by an independent panel. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months) | PFS is defined as the length of time from random assignment to disease progression or to death resulting from any cause, whichever occurred first, or to last contact. |
| Overall survival (OS) | For survival analysis participants are followed until death | OS is defined as the length of time from random assignment to death or to last contact. |
| Postchemotherapy radical (R0) surgical resection rate of metastases | Postchemotherapy radical (R0) surgical resection rate of metastases were evaluated every 8 weeks during treatment and during follow up (36 months) | Percentage of patients who undergo radical (R0) resection of metastases after achieving objective response to chemotherapy. |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Number of Participants with Adverse Events as a Measure of Safety and Tolerability were evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months) | During the full lenght of first-line treatment, number of enrolled patients reporting adverse events is recorded. Adverse events are evaluated according to National Cancer Institute Common Toxicity Criteria version 2.0. |
| Quality of life (QoL) | Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months) | Quality of life is assessed at the beginning of each treatment cycle using the Quality of Life Questionnaire of the European Organisation for Research and Treatment of Cancer (version 2.0). The QLQ-C30 questionnaire was analyzed with the global health status/quality-of-life scale as the primary end point and the other 10 scales as secondary end points. |
Countries
Italy
Outcome results
None listed