| General information |
| Database: | DB00950 |
| Objective: | The mammalian target of rapamycin (mTOR) plays a critical role in promoting tumor cell growth and is frequently activated in breast cancer. In preclinical studies, the antitumor activity of mTOR inhibitors is attenuated by feedback upregulation of AKT mediated in part by Insulinlike growth factor type 1 receptor (IGF1R). |
| Authors: | Ma CX, et al |
| Title: | a phase I trial of the IGF1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer. |
| Journal: | Breast Cancer Res Treat. |
| Year: | 2013 |
| PMID: | 23605083 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cixutumumab
|
| Target: | Insulinlike growth factor I receptor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | advanced breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Cixutumumab + temsirolimus |
| Study Type: | a phase I trial |
| Key Patients Feature: | patients with metastatic breast cancer refractory to standard therapies |
| Biomarker: | serum biomarkers |
| Biomark Analysis: | Compared with baseline, there was a significant increase in the serum levels of IGF1 (p < 0.001) and IGFBP3 (p = 0.019) on day 2. Compared with day 2, there were significant increases in the serum levels of IGF1 (p < 0.001), IGF2 (p = 0.001), and IGFBP3 (p = 0.019) on day 8 |
| Control Group Info: | single arm |
| Treatment Info: | A 3 + 3phase I design was chosen. Temsirolimus and Cixutumumab were administered intravenously on days 1, 8, 15, and 22 of a 4week cycle. Of the 26 patients enrolled, four did not complete cycle 1 because of disease progression (n = 3) or comorbid condition (n = 1) and were replaced. |
| Primary End Point: | maximumtolerated dose (MTD) and pharmacodynamic effects |
| Secondary End Point: | NA |
| Patients Number: | 26 |
| Trial Results |
| DLT_MTD: | The MTD was determined to be Cixutumumab 4 mg/kg and temsirolimus 15 mg weekly. Doselimiting toxicities (DLTs) included mucositis, neutropenia, and thrombocytopenia. |
| Objective Response Rate: | NA |
| 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): | Doselimiting toxicities (DLTs) included mucositis, neutropenia, and thrombocytopenia. Other adverse events included grade 1/2 fatigue, anemia, and hyperglycemia. |
| Conclusions: | Compared with baseline, there was a significant increase in the serum levels of IGF1 (p 0.001) and IGFBP3 (p = 0.019) on day 2. Compared with day 2, there they were significant increases in the serum levels of IGF1 (p 0.001), IGF2 (p = 0.001), and IGFBP3 (p = 0.019) on day 8. Aphase II study in women with metastatic breast cancer is ongoing |