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Randomized Open Label Study of Doxorubicin-based Chemotherapy Regimens, With and Without Sildenafil, With Exploratory Analysis of Intermediate Cardiac Markers

Phase 1
18 Years
Open (Enrolling)
Breast Cancer, Gastrointestinal Cancer, Genitourinary Cancer, Sarcoma, Gynecologic Cancer

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Trial Information

Randomized Open Label Study of Doxorubicin-based Chemotherapy Regimens, With and Without Sildenafil, With Exploratory Analysis of Intermediate Cardiac Markers

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.

Inclusion Criteria:

- Patients with any malignancy that is deemed appropriate for treatment with a
chemotherapy regimen incorporating a < 3 hour infusion of doxorubicin ≥ 40 mg/m2/dose
not more frequently than weekly. Single agent doxorubicin and combination
chemotherapy are allowed. The duration of treatment and the cumulative dose of
doxorubicin are determined by the chemotherapy regimen chosen for treatment of each
individual's disease and up to the discretion of the treating provider. Prior
doxorubicin-based regimen(s) allowed.

- At least 30 days since last doxorubicin before initiation of current
doxorubicin-based regimen

- Patients > 18 years of age

- ECOG performance status
- Able to understand and the willingness to sign a written informed consent. A signed
informed consent must be obtained prior to any study-specific procedures

Exclusion Criteria:

- Known congestive heart failure (active disease or history of)

- Left ventricular ejection fraction less than 50%

- Planned concurrent administration of other investigational agents

- Swallowing or absorption problems that might interfere with oral bioavailability of

- Known hypersensitivity to doxorubicin, sildenafil or any component of either agent

- Planned chronic nitrate or alpha blocker therapy

- Anticipated prolonged treatment with any strong CYP3A4 inhibitor: indinavir,
nelfinavir, ritonavir, saquinavir, clarithromycin, itraconazole, ketoconazole,
nefazodone, telithromycin

- Other relative contraindications to sildenafil as defined in the prescribing

- Myocardial infarction, stroke, or life-threatening arrhythmia within the last 6

- Coronary artery disease causing unstable angina

- Resting hypotension (BP <90/50) or hypertension (BP >170/110) despite
appropriate treatment

- Known retinitis pigmentosa

- Persisting or anticipated toxicity from prior therapy that might confound attribution
of on study adverse events

- Pregnant or nursing

- Known hearing loss

- History of priapism when exposed to PDE5 inhibitors (sildenafil, vardenafil,

- Other condition(s) that in the opinion of the investigator might compromise the
objectives of the study

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of concurrent sildenafil with doxorubicin-based chemotherapy

Outcome Description:

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.

Outcome Time Frame:

25 months

Safety Issue:


Principal Investigator

Andrew S. Poklepovic, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Virginia Commonwealth University


United States: Institutional Review Board

Study ID:




Start Date:

August 2011

Completion Date:

August 2017

Related Keywords:

  • Breast Cancer
  • Gastrointestinal Cancer
  • Genitourinary Cancer
  • Sarcoma
  • Gynecologic Cancer
  • Breast cancer
  • Gastrointestinal cancer
  • Genitourinary cancer
  • Sarcoma
  • Gynecologic cancer
  • Breast Neoplasms
  • Gastrointestinal Neoplasms
  • Urogenital Neoplasms
  • Sarcoma



Virginia Commonwealth University Richmond, Virginia