NCT01136031

Paclitaxel and Irinotecan in Advanced Gastric Cancer

A Phase I/II Trial of Second-line Chemotherapy With Paclitaxel and Irinotecan in Fluoropyrimidine- and Platinum-Pretreated Advanced Gastric Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: Seoul National University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

* 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.

Detailed description

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.

Conditions

• Advanced Gastric Cancer

Interventions

Type	Name	Description
DRUG	Paclitaxel and irinotecan	In phase I part, Level Paclitaxel (mg/m²) Irinotecan (mg/m²) 1. 100 100 2. 100 120 3. 135 120 4. 135 160 every 3 week

Timeline

• Start date: 2008-01-01
• Primary completion: 2011-06-01
• Completion: 2011-08-01
• First posted: 2010-06-03
• Last updated: 2015-05-20

Locations

1 site across 1 country: South Korea