| General information |
| Database: | DB00538 |
| Objective: | the primary objective of this study was to determine the rate of response to matuzumab in patients with recurrent, EGFRpositive ovarian, or primary peritoneal cancer. Secondary end points included safety and tolerability, time to tumor progression, duration of response, and overall survival. |
| Authors: | Seiden MV, et al |
| Title: | a phase II trial of EMD72000 (matuzumab), a humanized antiEGFR monoclonal antibody, in patients with platinumresistant ovarian and primary peritoneal malignancies. |
| Journal: | Gynecol Oncol. |
| Year: | 2007 |
| PMID: | 17126894 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | matuzumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | epithelial ovarian carcinoma or primary peritoneal carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multiinstitutional, openlabel, phase II trial with planned singlestage design. |
| Key Patients Feature: | recurrent platinumrefractory epithelial ovarian carcinoma or primary peritoneal carcinoma, measurable disease by computed tomographic (CT) scan (more than and equal to 2 cm or more than and equal to 1 cmby spiral CT), an Eastern Cooperative Oncology Group (ECOG) performancestatus of 0 or 1, age >18, and an anticipated survival of at least 3 months. Inaddition, patients were required not to have received any investigational orstandard antineoplastic agents, or radiation therapy within 30 days of initiatingtherapy and were required to have normal or nearnormal bone marrow, hepatic, renal, and cardiac function. Specifically, absolute neutrophil counts were to bemore than and equal to 1.5¡Á103/mm3, platelets more than and equal to 100¡Á103/mm3, and hemoglobin more than and equal to 10 g/dL. Inaddition, aspartate and alanine transaminases were all to be <2.5 times the upperlimit of normal (ULN) unless there was evidence of liver metastases, in whichcase less than and equal to 5¡ÁULN was allowed for transaminase values. Bilirubin was required tobe less than and equal to 2¡ÁULN, and serum creatinine less than and equal to 1.5¡ÁULN. Exclusion criteria includedtreatment with a prior monoclonal antibody or prior therapy that targeted theEGFR1 pathway. In addition, women with brain metastases, grade more than and equal to 2preexisting skin disorder, intercurrent immunosuppression, or comorbidillnesses were also excluded. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients initially were dosed with matuzumab 800 mg deliveredintravenously in normal saline over a 60min infusion on an everyweekschedule without planned interruption. Therapy was delivered on an outpatientbasis. |
| Primary End Point: | the rate of response |
| Secondary End Point: | safety and tolerability, time to tumor progression, duration of response, and overall survival. |
| Patients Number: | 37 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | There were no formal responses (RR=0%, 95% CI: 0-9.5%), although 7 patients (21%) were on therapy for more than 3 monthswith stable disease |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | For the intentiontotreat population, median time to progression was 54 days (95% CI: 51, 59) . For the perprotocol population, median time to progression was 58 days (95% CI: 53, 103) |
| Median OS A vs. C: | For intentiontotreat population, median overall survival was 10.3 months (95% CI: 6.77, 13.90). For the perprotocol population, median overall survival was 13.3 months (95% CI: 7.87, 13.90). |
| Adverse Event(agent arm): | Serious adverse events were typically due to progressive cancer and included increase in ascites, small botheyl obstruction, and pericardial effusion. In three patients, there were five grade 3 serious adverse events thought to be possibly associated with matuzumab, including nausea, vomiting, abdominal pain, dehydration, and increased amylase thought to be due to pancreatitis. There was also one episode of a central retinal artery occlusion. |
| Conclusions: | Matuzumab at the dose and schedule selected is well tolerated. In this population of very heavily pretreated patients with epithelial ovarian and primary peritoneal malignancies, there was no evidence of significant clinical activity when matuzumab was administered as monotherapy. |