Entry Detail
| General information | |
| Database: | DB00203 |
| Objective: | Activation of the vascular endothelial growth factor receptor (VEGFR) and the oncogenic Src pathway has been implicated in the development of castrationresistant prostate cancer (CRPC) in preclinical models. Cediranib and dasatinib are multikinase inhibitors targeting VEGFR and Src respectively.phase II studies of cediranib and dasatinib in CRPC have shown single agent activity.(interrupted prematurely) |
| Authors: | Spreafico A, et al |
| Title: | A randomizedphase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients. |
| Journal: | Invest New Drugs. |
| Year: | 2014 |
| PMID: | 24788563 |
| Trial Design | |
| Clinical Trial Id: | NCT01260688 |
| Agent: | dasatinib |
| Target: | Protooncogene tyrosineprotein kinase SRC Abl Protooncogene tyrosineprotein kinase LCK Protooncogene tyrosineprotein kinase Fyn |
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castration resistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | cediranib + dasatinib |
| Study Type: | a multicenter, randomizedphase II study |
| Key Patients Feature: | docetaxel resistant, castration resistant prostate cancer patients |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | cediranib alone |
| Treatment Info: | patients were randomized to arm A: cediranib alone (20 mg/day) versus arm B: cediranib (20 mg/day) plus dasatinib (100 mg/day) given orally on 4week cycles. |
| Primary End Point: | 12week progression free survival (PFS). Patient reported outcomes were evaluated using Functional Assessment of Cancer TherapyProstate (FACTP) and Present Pain Intensity (PPI) scales. |
| Secondary End Point: | Correlative studies of bone turnover markers (BTM), including bone alkaline phosphate (BAP) and serum betaC telopeptide (BCTx) were serially assayed. |
| Patients Number: | 22 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | FACTP and PPI scores did not significantly change in either arm. No correlation between BTM and PFS was seen in either arm. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Ttheylveweek PFS was 73 % in arm A versus 18 % in arm B (p = 0.03). Median PFS in months (arm A versus B) was: 5.2 versus 2.6 (95 % CI: 1.96.5 versus 1.4not reached). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most common grade 3 toxicities were hypertension, anemia and thrombocytopenia in arm A and hypertension, diarrhea and fatigue in arm B. One treatmentrelated death (retroperitoneal hemorrhage) was seen in arm A. |
| Conclusions: | Although limited by small numbers, this randomized study showed that the combination of VEGFR and Src targeted therapy did not result in improved efficacy and may be associated with a worse outcome than VEGFR targeted therapy alone in patients with CRPC. |