| General information |
| Database: | DB00528 |
| Objective: | Bevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF1¦Á levels, a resistance mechanism for antiangiogenics, and targets the PI3kinase/AKT/mTOR axis, commonly aberrant in these tumors. |
| Authors: | PihaPaul SA, et al |
| Title: | Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus. |
| Journal: | Oncotarget. |
| Year: | 2014 |
| PMID: | 24742900 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | vulvar carcinoma,vaginal carcinoma, ovarian, primary peritoneal, or fallopian tube carcinoma,endometrial carcinoma,cervical cancer |
| Cancer Subtype: | Advanced gynecologic malignancies |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | bevacizumab and temsirolimus |
| Study Type: | part of a phase I study |
| Key Patients Feature: | pts with Primary Organ SiteFallopian Tube Vagina Ovarian High grade serous^ Low grade serous Endometroid# Clear Cell Transitional Cell Undifferentiated Carcinoma, Mullerian# Uterus Epithelial Carcinosarcoma Clear Cell Cervix Squamous Adenocarcinoma Neuroendocrine |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | DoseEscalation Schedule and regimens were listed in table 2;patients with gynecologic cancers were treated as part of a phase I study of bevacizumab and temsirolimus |
| Primary End Point: | antitumor activity and safety |
| Secondary End Point: | NA |
| Patients Number: | 41 |
| Trial Results |
| DLT_MTD: | Full FDAapproved doses of both drugs (bevacizumab 15mg/kg IV Q3weeks and temsirolimus 25mg IV weekly) were administered without doselimiting toxicity. |
| Objective Response Rate: | Eight patients (20%) achieved stable disease (SD) > 6 months and 7 patients (17%), a partial response (PR) [total = 15/41 patients (37%)]. Eight of 13 patients (62%) with highgrade serous histology (ovarian or primary peritoneal) achieved SD > 6 months/PR. |
| 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): | Grade 3 or 4 treatmentrelated toxicities included: thrombocytopenia (10%), mucositis (2%), hypertension (2%), hypercholesterolemia (2%), fatigue (7%), elevated aspartate aminotransferase (2%), and neutropenia (2%). Twentynine patients (71%) experienced no treatmentrelated toxicity greater than grade 2. |
| Conclusions: | Bevacizumab and temsirolimus was well tolerated. Thirtyseven percent of heavilypretreated patients achieved SD 6 monthsPR, suggesting that this combination warrants further study. |