| General information |
| Database: | DB00529 |
| Objective: | egylated liposomal doxorubicin (PLD) is active in breast, endometrial, and ovarian cancer. Preclinical data suggest that the combination of PLD with a mammalian target of rapamycin (mTOR) inhibitor has an additive effect. The safety and recommendedphase two dose (RPTD) of temsirolimus in combination with PLD were assessed. |
| Authors: | BoersSonderen MJ, et al |
| Title: | Temsirolimus and pegylated liposomal doxorubicin (PLD) combination therapy in breast, endometrial, and ovarian cancer:phase Ib results and prediction of clinical outcome with FDGPET/CT. |
| Journal: | Target Oncol. |
| Year: | 2014 |
| PMID: | 24577626 |
| Trial Design |
| Clinical Trial Id: | NCT0098263 |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | breast cancer, endometrial cancer, and ovarian cancer |
| Cancer Subtype: | advanced breast, endometrial, and ovarian cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Temsirolimus and pegylated liposomal doxorubicin (PLD) combination therapy |
| Study Type: | phase Ib results and prediction of clinical outcome with FDGPET/CT |
| Key Patients Feature: | patients with advanced breast, endometrial, and ovarian cancer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with increasing doses of temsirolimus (10, 15, or 20 mg once weekly) and PLD (30 or 40 mg/m(2) once every 4 weeks). PLD was initiated 2 weeks after start of temsirolimus. FDGPET/CT was performed at baseline, after 2 and 6 weeks. |
| Primary End Point: | DLT, RP2D, frequent treatmentrelated toxicities. |
| Secondary End Point: | Standardized uptake values (SUV), metabolic volume, and total lesion glycolysis (TLG, SUV ¡Á metabolic volume) were calculated. |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | The RPTD was 15 mg temsirolimus and 40 mg/m(2) PLD. Doselimiting toxicities (DLT) were thrombocytopenia grade 3 with nose bleeding and skin toxicity grade 3. |
| Objective Response Rate: | Changes in TLG after 2 weeks predicted partial response (PR) after 10 weeks (p = 0.037). A rise in SUV between the second and sixth week predicted progression (PD) (p = 0.034) and was associated with worse progression free survival (PFS) (HR 1.068; p = 0.013). |
| 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): | NA |
| Conclusions: | Early response evaluation with FDGPETCT may predict subsequent radiological PR and PD |