Entry Detail
| General information | |
| Database: | DB01024 |
| Objective: | the Trifunctional Antihuman epidermal growth factor receptor 2 * AntiCD3 Antibody Ertumaxomab inMetastatic Breast Cancer |
| Authors: | Philipp Kiethey |
| Title: | Phase I trial of the trifunctional antihuman epidermal growth factor receptor 2 x antiCD3 antibody ertumaxomab in metastatic breast cancer. |
| Journal: | clinical cancer research |
| Year: | 2006 |
| PMID: | 16707606 |
| Trial Design | |
| Clinical Trial Id: | NCT00522457 |
| Agent: | ertumaxomab |
| Target: | Receptor proteintyrosine kinase erbB2 Tcell surface glycoprotein CD3 epsilon chain CD3 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a German multicenter, uncontrolled, sequential doseescalating, phase I study. |
| Key Patients Feature: | Female patients with histologically confirmed metastatic breast cancer expressing human epidermal growth factor receptor 2/neu who had no indication for cytoreductive systemic treatment at the time of enrollment were eligible for the study. human epidermal growth factor receptor 2/neu expression was defined as theyak to strong positivity (1+, 2+, and 3+) by standard immunohistochemistry methods (Dakotest). Patients were required to be 18 to 75 years of age, have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, a life expectancy of at least 6 months, and adequate hematological (hemoglobin, >9 g/dL; platelets, >100/nL; white blood count, >3 and <13/nL), renal (creatinine, <2 mg/dL), and hepatic function (alanine aminotransferase, aspartate aminotransferase, and/or gglutamyltransferase <2.5 upper limit of normal, in case of liver metastases, alanine aminotransferase, aspartate aminotransferase, and/ or gglutamyltransferase <5 upper limit of normal, bilirubin <2 upper limit of normal). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | NA |
| Treatment Info: | Three ascending doses of ertumaxomab (10200 Ag) were administered i.v. on day 1, 7 ¡À 1, and 13 ¡À 1. |
| Primary End Point: | The safety and tolerability of ertumaxomab and the identification of the maximum tolerated dose (MTD) were the primary objectives. |
| Secondary End Point: | antitumor activity, measurement of different immunologic variables [cytokine release, hematological cell populations, and human antimouse/antirat antibody. |
| Patients Number: | 17 |
| Trial Results | |
| DLT_MTD: | 10100100 ¦Ìg |
| Objective Response Rate: | Antitumor response was seen in 5 out of 15 evaluable patients (one with a complete response, two with partial responses, two with stable disease) at dose levels of > or = 100 microg. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | One patient (no. 15) developed severe hypotension and respiratory distress syndrome after the second dose (200 Ag); one patient (no. 13) experienced a systemic inflammatory response syndrome after the second infusion (150 Ag), which was accompanied by other severe side effects such as disseminated intravascular coagulation, dyspnea, acute liver failure, and renal failure. These two serious adverse events were fully reversible. Aggravation of congestive heart failure was seen in one patient (no. 14) with preexisting ventricular dysfunction, following the administration of the third dose (200 Ag), however, the relation to treatment was uncertain. |
| Conclusions: | Treatment with triple infusions of ertumaxomab yields a strong immunologic response. Doses up to 100 Ag can be safely infused with close monitoring of patients. The observed clinical responses are encouraging and indicate antitumor efficacy. |