Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02520063 | Combination of Letrozole, Everolimus and TRC105 in Postmenopausal Women With Hormone-Receptor Positive and Her2 Negative Breast Cancer | PHASE1 | COMPLETED | 15 | — | — | Feb 1, 2015 | Dec 1, 2022 | Feb 6, 2026 | 1 | United States |
This outcome will report the number of patients who experienced a dose-limiting Toxicity (DLT) in Phase I Cohort 1, Phase I Cohort 2, and Phase I Cohort -1. A DLT was defined as: 1. A grade 3 or 4 non-hematologic toxicity except anorexia, alopecia, nausea (which is not refractory to antiemetics), fatigue, and fever without neutropenia; 2. Failure to recover to baseline (except alopecia) after delaying the next dose by more than 14 days; 3. Grade 3 or 4 neutropenia complicated by fever \>38.5°C or infection, or grade 4 neutropenia of ≥7 days duration; or 4. Grade 4 thrombocytopenia, or grade 3 thrombocytopenia complicated by hemorrhage. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 out of the first 3 or 1 out of a total of 6 patients experience DLT during the first cycle of therapy; this dose level will be the recommended phase 2 dose (RP2D) in the Phase II Group.
| Arm | Type | Description |
|---|---|---|
| Phase I Cohort 1 | EXPERIMENTAL | Letrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks |
| Phase I Cohort 2 | EXPERIMENTAL | Letrozole 2.5 mg PO daily until surgery, everolimus 10 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks |
| Phase I Cohort -1 | EXPERIMENTAL | Letrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 10 mg/kg IV q 2 weeks for 24 weeks |
| Phase II | EXPERIMENTAL | Letrozole 2.5 mg PO daily until surgery, everolimus 5 or 10 mg PO daily for 24 weeks, and TRC105 15 or 10 mg/kg IV q 2 weeks for 24 weeks. Dose and regimen to be determined based on data from the phase I component. |
| Name | Type | Description |
|---|---|---|
| Letrozole | DRUG | A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study. |
| Everolimus | DRUG | The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery. |
| TRC105 | DRUG | The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery. |
Inclusion Criteria: * Recent diagnosis of hormone receptor positive and HER2 negative breast cancer. * Stage 2 and 3 hormone receptor positive and HER2 negative breast cancer (stage T2-4 but not inflammatory, N0-2, M0). * Histological grade I, II or III according to the modified Bloom Richardson sc...