A Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer
- Registration Number
- NCT01304602
- Lead Sponsor
- University of Kansas Medical Center
- Brief Summary
This phase I trial will use the combination of irinotecan and BKM120 in patients with advanced colorectal cancer who have failed on or have become intolerant of at least one line of therapy for advanced colorectal cancer and who are candidates for irinotecan therapy.
- Detailed Description
Although survival of patients with advanced colorectal cancer has improved in the last two decades, the overwhelming majority of these patients will still succumb from this disease. It is the third most commonly diagnosed malignancy in the United States. We have witnessed significant leaps in understanding colorectal cancer carcinogenesis as well as in identification of a number of prognostic and predictive factors associated with this malignancy. With the use of combination chemotherapy and the addition of targeted agents, the median survival of patients with advanced colorectal cancer has improved from 4-6 months with supportive care to over 2 years.
Molecularly directed therapy for cancer holds promise to a more personalized approach to treating cancer. Increase understanding of tumorigenesis has resulted in the identification of promising targets of therapy for more strategic approach to treatment of this malignancy. However, even with the development of molecularly directed treatment, the therapy for advanced colorectal cancer remains to be primarily palliative in nature to majority of patients. There is definite need for a more effective therapy, agents with more acceptable toxicity profiles, and drugs that could be administered without significant demand on time and activity for individual patients receiving these drugs.
This is a phase I trial of the combination of irinotecan and BKM120 in patients with advanced colorectal cancer who have failed on or have become intolerant of at least one line of therapy for advanced colorectal cancer and who are candidates for irinotecan therapy. This study will attempt to estimate the Maximum Tolerated Dose of the combination of irinotecan and BKM120.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Irinotecan + BKM120 BKM120 Irinotecan + BKM120 at the assigned cohort dose level. Irinotecan + BKM120 Irinotecan Irinotecan + BKM120 at the assigned cohort dose level.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose 28 days The maximum tolerated dose will be defined as the dose level prior to the dose level in which dose-escalation was stopped based on dose-limiting toxicities (DLTs). DLTs are based on specific adverse events specified in the study protocol. DLTs will be assessed during the first two cycles of treatment (28 days total).
- Secondary Outcome Measures
Name Time Method Biological half life of BKM120 up to 25.5 hours post dose of irinotecan The biological half life of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.
area under the plasma concentration versus time curve (AUC) of BKM120 up to 25.5 hours post dose of irinotecan The AUC of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.
area under the plasma concentration versus time curve (AUC) of irinotecan up to 25.5 hours post dose of irinotecan Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.
Change in tumor size baseline, and every 8 weeks Disease will be assessed at baseline and then every four cycles (8 weeks) by CT or MRI. Response will be assessed following RECIST criteria. Patients will be categorized as complete response, partial response, progressive disease, stable disease, or unknown.
Peak Plasma Concentration (Cmax) of irinotecan up to 25.5 hours post-dose of irinotecan Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.
biological half-life of irinotecan up to 25.5 hours post dose of irinotecan Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.
Peak Plasma Concentration (Cmax) of BKM120 up to 25.5 hours post-dose of irinotecan The Cmax of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.
Trial Locations
- Locations (1)
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States