Entry Detail
| General information | |
| Database: | DB00368 |
| Objective: | Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects. |
| Authors: | Mayr M, et al |
| Title: | Phase I study of imatinib, cisplatin and 5fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma. |
| Journal: | BMC Cancer. |
| Year: | 2012 |
| PMID: | 23228190 |
| Trial Design | |
| Clinical Trial Id: | NCT00601510 |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | advanced esophageal or gastric adenocarcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | imatinib, cisplatin and 5fluoruracil or capecitabine |
| Study Type: | multicenter open labelphase I study |
| Key Patients Feature: | Inclusion criteria weredefined: histologically confirmed advanced esophageal orgastric adenocarcinoma, presence of at least one measureable lesion according to RECIST criteria, adequatehematopoietic, hepatic and renal function - defined as:white blood cell (WBC) count more than and equal to 3000/¦Ìl, absolute neutrophil count (ANC) more than and equal to 2000/¦Ìl, platelets more than and equal to 100000/¦Ìl, hemoglobin level more than and equal to 9.0 g/dl, total bilirubin < 2 times theupper limit of normal (ULN) , SGOT and SGPT < 2.5times the UNL (or < 5 x ULN if hepatic metastases arepresent), glomerular filtration rate (GFR) more than and equal to 60ml/min, Eastern Cooperative Oncology Group (ECOG) performance status less than and equal to 2. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Thirtyfive patients received cisplatin (60 mg/m(2) d1 q 3w)/ capecitabine (1250 mg/m(2) bid d114 q 21) or cisplatin (50 mg/m(2) d1 q 2w)/ 5fluoruracil (2 g/m(2) d1, q 1w). Imatinib was started d 4 with dose escalation from 300 to 700 mg QD in 100 mg steps. |
| Primary End Point: | safety and tolerability in order to determine the maximum tolerable dose (MTD), DLT. |
| Secondary End Point: | The preliminary antitumor activity |
| Patients Number: | 35 |
| Trial Results | |
| DLT_MTD: | Dose limiting toxicity (DLT) was defined as grade 3 neutropenia with fever or infection; grade 4 neutropenia persisting more than and equal to 7 days; grade 3 thrombocytopenia with bleeding or grade 4 thrombocytopenia > 7 days; any nonhematological toxicity grade 3 or 4 except alopecia, nausea and vomiting; increase in urinary retention parameters more than and equal to grade 2; peripheral sensory neuropathy more than and equal to grade 3.At imatinib dose level 1 (300mg) one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). The MTD was the highest dose of imatinib that resulted in DLT in fetheyr than one in 3 or 2 in 6 patients per cohort. Only toxicities during the first three cycles were considered for defining the MTD. Analysis of the toxicity data from treatment of 35 patients in a 3patientcohort doseescalating design revealed 600 mg imatinib as the MTD. |
| Objective Response Rate: | Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients. |
| Disease Control Rate: | 0.7 |
| Median Time to Progression: | 19 weeks (range 6-57). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 59 weeks (range 22-103). |
| Adverse Event(agent arm): | Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). |
| Conclusions: | Combination of imatinib and chemotherapy is well tolerated. Response rates they were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib. |