Paclitaxel and Irinotecan in Advanced Gastric Cancer (TI-2ndAGC)
|ClinicalTrials.gov Identifier: NCT01136031|
Recruitment Status : Completed
First Posted : June 3, 2010
Last Update Posted : May 20, 2015
- Usually the combination of fluoropyrimidine with platinum is used as a first line chemotherapy (for example, 5-FU+cisplatin, capecitabine+cisplatin, S-1+ cisplatin, 5-FU+oxaliplatin) in advanced gastric cancer.
- After failure with this combination, taxane-based regimen or irinotecan-based regimen is usually used. But, as a second-line regimen, the combination of topoisomerase inhibitor with taxane has not been fully evaluated until now.
- So we designed this phase I/II study to evaluate the efficacy and toxicity of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine and platinum-pretreated advanced gastric cancer.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Gastric Cancer||Drug: Paclitaxel and irinotecan||Phase 1 Phase 2|
In gastric cancer, several active chemotherapeutic agents have been introduced. Fluoropyrimidine, platinum, taxane and topoisomerase inhibitor are the most commonly used agents. Many available single or combination regimens are existed. But, there is no standard palliative chemotherapy regimen as a first line treatment in unresectable advanced gastric cancer. Thereafter there is also no standard second line regimen.
Usually the combination of fluoropyrimidine with platinum is used as a first line chemotherapy (for example, 5-FU+cisplatin, capecitabine+cisplatin, S-1+ cisplatin, 5-FU+oxaliplatin). After failure with this combination, taxane-based regimen or irinotecan-based regimen is usually used. But, as a second-line regimen, the combination of topoisomerase inhibitor with taxane has not been fully evaluated until now.
In some studies using docetaxel and irinotecan combination in gastric cancer, the toxicity is highly concerned. (Jatoi A et al. 2002, Lordick F etl al. 2003, S Enrech et al. 2003, Chang HM et al. 2003) The combination of paclitaxel and irinotecan in gastric cancer is evaluated in two studies until now as far as we know (K Kobayashi et al. 2006, Hecht JR et al. 2003). These are phase I/II design and used this combination as first or second line treatment of gastric cancer. The response rate is 29.6% and 27% respectively. In one study, grade 3,4 hematologic toxicity is 33.3%. The dosing schedule is different between these two studies.
In one study, paclitaxel 50mg/m2 and irinotecan 50mg/m2 is used day 1and day 8 every 3 weeks. In the other study, paclitaxel 100mg/m2 and irinotecan 225mg/m2 is used every 3 weeks.
In these studies, the state of UGT1A1 polymorphism of enrolled patients has not been reported. Recently it is well known that the UGT1A1 polymorphism influences on the toxicity profile of irinotecan, e,g. myelosuppression and diarrhea. If a patient with UGT1A1*28 (7/7 homozygosity) is included in the low level of phase I period, the MTD of irinotecan might be set up in low dose without showing sufficient efficacy.
We think that it may be of deserve to evaluate the efficacy of paclitaxel and irinotecan combination regimen in gastric cancer patients and it is necessary to conduct phase I study to find out the accurate MTD of this regimen after considering the UGT1A1 polymorphism of patients.
So we designed this phase I/II study to evaluate the efficacy and toxicity of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine and platinum-pretreated advanced gastric cancer.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Second-line Chemotherapy With Paclitaxel and Irinotecan in Fluoropyrimidine- and Platinum-Pretreated Advanced Gastric Cancer|
|Study Start Date :||January 2008|
|Primary Completion Date :||June 2011|
|Study Completion Date :||August 2011|
|Experimental: Paclitaxel and irinotecan||
Drug: Paclitaxel and irinotecan
In phase I part, Level Paclitaxel (mg/m²) Irinotecan (mg/m²)
every 3 week
- Dose-limiting toxicity (phase I part) [ Time Frame: during first cycle (first 3 week) ]
- response rate (phase II part) [ Time Frame: every 2 cycles response evaluation ]
- recommended phase II dose [ Time Frame: after the determining MTD ]
- time to progression [ Time Frame: at the time of disease progression ]
- overall survival [ Time Frame: at the time of death ]
- toxicities [ Time Frame: every time of physical exam and laboratory evaluation ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01136031
|Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Korea, Republic of, 110-744|
|Principal Investigator:||Do-Youn Oh, MD, PhD||Seoul National University Hospital|