| General information |
| Database: | DB00434 |
| Objective: | To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as firstline treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). |
| Authors: | Rao S, et al |
| Title: | Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. |
| Journal: | Br J Cancer. |
| Year: | 2008 |
| PMID: | 19238629 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | matuzumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | gastric cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the stomach or lower third of the oesophagus |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | epirubicin, cisplatin and capecitabine plus matuzumab |
| Study Type: | phase I open label study |
| Key Patients Feature: | Eligibility requirements included histologically confirmed adenocarcinoma of the stomach or lotheyr third of the oesophagus, locallyadvanced, metastatic or recurrent disease, measurable diseaseby computed tomography (CT), EGFR expression in tumourtissue, normal cardiac function defined by left ventricular ejection fraction, Karnofsky performance status (KPS) X60%, lifeexpectancy 412 weeks, no prior chemotherapy at all, no radiotherapy or major surgery within 4 weeks before the first studytreatment, adequate baseline bone marrow and liver function, aglomerular filtration rate 460 ml min 1, no severe uncontrolledcomorbidities and signed informed consent. |
| Biomarker: | NA |
| Biomark Analysis: | At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT3. |
| Control Group Info: | single arm |
| Treatment Info: | This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m(2), cisplatin 60 mg m(2) on day 1 and capecitabine 1000 mg m(2) daily). patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twentyone patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. |
| Primary End Point: | DLT, MDT, ORR, DCR and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 45 |
| Trial Results |
| DLT_MTD: | The main doselimiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus800 mg matuzumab weekly was the maximumtolerated dose (MTD).The MTD of matuzumab in combination with ECX was 800 mg weekly |
| Objective Response Rate: | Objective response rates of 65% (95%confidence interval (CI): 43-82), disease stabilisation of 25% (95% CI: 11-47) and a disease control rate (CRtPRtSD) of 90%were achieved overall |
| Disease Control Rate: | 0.9 |
| Median Time to Progression: | 5.2 months (95% CI: 3.0- 16.0). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The main doselimiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximumtolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. |
| Conclusions: | The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was welltolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT3. |