| General information |
| Database: | DB00235 |
| Objective: | Recent data indicate that there is a significant crosstalk between the PI3K/Akt/mTOR and androgen receptor signaling pathways. They evaluated safety and tolerability as well as potential drugdrug interaction of ridaforolimus, a mammalian target of rapamycin (mTOR) inhibitor, when combined with the androgen receptor inhibitor bicalutamide in patients with asymptomatic, metastatic castrationresistant prostate cancer. |
| Authors: | Meulenbeld HJ, et al |
| Title: | Tolerability, safety and pharmacokinetics of ridaforolimus in combination with bicalutamide in patients with asymptomatic, metastatic castrationresistant prostate cancer (CRPC). |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2013 |
| PMID: | 23921574 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | ridaforolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | ridaforolimus+ bicalutamide |
| Study Type: | A prospective, openlabel, international, multicenter safety leadin trial |
| Key Patients Feature: | Twelve patients were enrolled in the safety leadin including 1 screen failure. The median age was 63 years (range 58-72 years) |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with the combination of ridaforolimus 30 mg/day for 5 consecutive days each week and bicalutamide 50 mg/day. Ridaforolimus pharmacokinetics was assessed with and without bicalutamide. |
| Primary End Point: | Tolerability, safety and pharmacokinetics |
| Secondary End Point: | NA |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | Dose reductions were required in 7 patients. Three of the 11 patients experienced a doselimited toxicity, 1 with Grade 3 hyperglycemia and 2 with Grade 2 stomatitis leading to <75 % of planned ridaforolimus dose during the first 35 days of study treatment. |
| Objective Response Rate: | Ten out of 11 patients had both baseline PSA and postbaseline PSA measurements within 12 weeks. Four patients (36 %) had more than and equal to 30 % PSA decline within 12 weeks, while 5 patients (45 %) had persistently increasing PSA within 12 weeks of treatment |
| 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): | The most common drugrelated AEs were fatigue (n = 8), rash (n = 6), stomatitis (n = 5), hypercholesterolemia (n = 5), dysgeusia (n = 5), anorexia (n = 5) and pneumonitis (n = 5) (Table 2). Four patients (36.4 %) had at least one Grade 3 or higher drugrelated treatmentemergent adverse event (TEAE). |
| Conclusions: | Although there was no evidence of a clinically relevant pharmacological drugdrug interaction, the occurrence of doselimiting toxicities in 3 of 11 evaluable patients at a reduced dose of ridaforolimus of 30 mgday suggests that this combination may not be well suited for asymptomatic or minimally symptomatic prostate cancer patients. |