Doxorubicin With or Without Sildenafil, With Analysis of Cardiac Markers
Sildenafil increases the therapeutic effect of doxorubicin used as treatment for cancers of solid tumors through both an increase in anti-tumor effects and protection from cardiac toxicity.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Open Label Study of Doxorubicin-based Chemotherapy Regimens, With and Without Sildenafil, With Exploratory Analysis of Intermediate Cardiac Markers|
- Safety of concurrent sildenafil with doxorubicin-based chemotherapy [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]Sildenafil will be administered at least 7 days prior to scheduled first dose of doxorubicin and continue daily dosing through 2 weeks after last doxorubicin dose. Multiple biomarkers as candidate early markers of anthracycline-induced cardiotoxicity will be tested.
- Comparison of candidate early markers of cardiac injury [ Time Frame: 37 months ] [ Designated as safety issue: No ]The fluctuation in the levels of biomarkers including novel ultra sensitive troponins and BNP, as well as tissue doppler imaging studies with echocardiography will analyzed.
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Sildenafil + doxorubicin
Sildenafil, 100 mg capsule, once daily at least 7 days prior to scheduled first dose of doxorubicin and continue daily dosing through 2 weeks from scheduled last doxorubicin dose.
As prescribed by treating providerDrug: Sildenafil
100 mg capsule once daily at least 7 days prior to scheduled first dose of doxorubicin and continue daily dosing through 2 weeks from scheduled last doxorubicin dose
Other Name: Viagra, Revatio
Active Comparator: Doxorubicin-based chemotherapy
Doxorubicin-based therapy will commence and continue as clinically indicated and as prescribed by treating provider.
As prescribed by treating provider
Definitive study of sildenafil enhancement of anthracycline anticancer effects and cardioprotection would require a randomized, placebo-controlled trial involving large numbers of patients and many years of follow-up. It is appropriate to demonstrate that concurrent administration of sildenafil and doxorubicin is safe and tolerable. Second, in definitive studies it might be helpful to incorporate early markers of cardiac injury in order to gain early insight into cardioprotective effects, but there are no such established markers. As a correlative study, multiple intermediate markers will be tested. In order to investigate these candidate markers it is appropriate to study patients receiving doxorubicin alone, as early markers of injury may not be apparent in patients treated with the combination. In order to accomplish these two goals the trial is a randomized trial involving a sildenafil/doxorubicin group and a doxorubicin group.
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298-0037|
|Principal Investigator:||Andrew S. Poklepovic, MD||Virginia Commonwealth University|