| General information |
| Database: | DB00432 |
| Objective: | To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)targeting monoclonal antibody matuzumab combined with highdose 5fluorouracil, leucovorin and cisplatin (PLF) in the firstline treatment of patients with EGFRpositive advanced gastric and esophagogastric adenocarcinomas. |
| Authors: | Trarbach T, et al |
| Title: | Phase I study of matuzumab in combination with 5fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 22763610 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | matuzumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | gastric cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | EGFR expressing advanced, recurrent or metastatic gastric or gastroesophagealadenocarcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | matuzumab + 5fluorouracil, leucovorin and cisplatin (PLF) |
| Study Type: | openlabel, phase I, singlecenter study |
| Key Patients Feature: | patients were eligible for inclusion if they were between 18and 72 years of age, had histologically confirmed, EGFRexpressing (determined by immunohistochemistry), advanced, recurrent or metastatic gastric or gastroesophagealadenocarcinoma, a life expectancy >12 weeks, a KarnofskyPerformance Status (KPS) of at least 60, and at least oneevaluable lesion, according to Response Evaluation CriteriaIn Solid Tumors (RECIST) [40]. Patients also had to haveadequate liver (bilirubin <2 x upper limit of normal [ULN], ALT/AST <2 x ULN or tumorrelated ALT/AST <5 x ULN)and bone marrow (WBC >3, 000/ul, platelets >100, 000/ul, hemoglobin >9 g/dl) function, a creatinine clearance rate of60 ml/minute or better, complete recovery from any relevantside effects of previous treatments and be practicing effective contraception throughout study participation if appropriate |
| Biomarker: | EGFR |
| Biomark Analysis: | NA |
| Control Group Info: | two matuzumab dose groups with the first cohort of patients receiving 400 mg matuzumab in combination with PLF;the next cohort of patients received 800 mg matuzumab |
| Treatment Info: | patients were treated in two matuzumab dose groups with the first cohort of patients receiving 400 mg matuzumab in combination with PLF. Based on the safety observations the next cohort of patients received 800 mg matuzumab. The study was conducted in two parts, withphase A, designed to assess the safety and tolerability of the combination, andphase B designed to be a treatment continuation for those patients benefiting from treatment. Treatment cycles were 7 weeks each. Each patient received the dose of matuzumab they were assigned to at study entry for the duration of the study. |
| Primary End Point: | DLTs, MDT, AE |
| Secondary End Point: | NA |
| Patients Number: | 15 |
| Trial Results |
| DLT_MTD: | For reasons of safety, enrollment of patients for treatment with the 800 mg dose only started after completion of treatment of, and evaluation of safety (less than and equal to 2 protocol defined doselimiting toxicities [DLTs] among 6 patients) for, patients receiving the 400 mg matuzumab dose. The maximum tolerated dose (MTD) was defined as the highest dose that induced a DLT in not more than 1 of 6 patients.the MTD was not reached. |
| Objective Response Rate: | No patient achieved a complete response but confirmed and nonconfirmed response rates of 28.6 % and 25.0 % and 57.1 % and 37.5 % were achieved in the 400 mg dose and 800 mg matuzumab dose groups respectively |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.1 months. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent AEs were diarrhea and acne in 11 patients (73.3 %) each, followed by nausea in 10 patients (66.7 %), stomatitis and fatigue in 9 patients (60 %) each. Nausea and vomiting were more common in the 800 mg than 400 mg matuzumab group. Grade 3 or 4 AEs occurring in more than and equal to 2 patients were thrombosis (20 %), leukopenia (13.3 %) and neutropenia (13.3 %). Of these only one AE was classified as grade 4; leukopenia in a patient in the 400 mg matuzumab dose group. |
| Conclusions: | Matuzumab, in combination with PLF, demonstrated an acceptable safety profile with modest antitumor activity. |