Doxorubicin With or Without Sildenafil, With Analysis of Cardiac Markers

NCT01375699 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-13419NCI-2011-0098
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Gastrointestinal Cancer; Genitourinary Cancer; Sarcoma; Gynecologic Cancer

Keywords

Breast cancer; Gastrointestinal cancer; Genitourinary cancer; Sarcoma; Gynecologic cancer

Outcome Measures

Primary Outcomes (2)

• Safety of concurrent sildenafil with doxorubicin-based chemotherapy

  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.

  25 months

• The difference in left ventricular ejection fraction (LVEF) between arms

  A repeated measures analysis of variance (ANOVA) will be used to compare the LVEF between Arm 1 and Arm 2 over all visits. A pooled t-test will also be performed to determine the change in LVEF between first and last visits.

  4 years

Secondary Outcomes (1)

• Comparison of candidate early markers of cardiac injury

  37 months

Study Arms (2)

Sildenafil + doxorubicin

EXPERIMENTAL

Patients receive sildenafil citrate PO QD\* beginning at least 2 days prior to scheduled first dose of doxorubicin hydrochloride and continuing until 2 weeks after last scheduled dose of doxorubicin hydrochloride. Patients also receive doxorubicin hydrochloride IV as clinically indicated and as prescribed by treating provider. NOTE: \*Patients receive sildenafil citrate PO TID on days that doxorubicin hydrochloride is also administered.

Drug: Doxorubicin; Drug: Sildenafil

Doxorubicin-based chemotherapy

ACTIVE COMPARATOR

Patients receive doxorubicin hydrochloride IV as clinically indicated and as prescribed by treating provider.

Drug: Doxorubicin

Interventions

Doxorubicin DRUG

As prescribed by treating provider.

Also known as: 123127, Doxorubicin Hydrochloride, 3-Hydroxyacetyldaunorubicin Hydrochloride, Adriamycin Hydrochloride, ADM, Adriacin, Adriamycin

Doxorubicin-based chemotherapy; Sildenafil + doxorubicin

Sildenafil DRUG

Given PO, by mouth

Also known as: Viagra, Revatio, Sildenafil Citrate, 171599-83-0

Sildenafil + doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with any malignancy that is deemed appropriate for treatment with a chemotherapy regimen incorporating a \< 3-hour infusion of doxorubicin \>= 40 mg/m\^2/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, unless the most recent prior doxorubicin-based regimen resulted in documented refractory disease
• At least 30 days since last doxorubicin before initiation of current doxorubicin-based regimen
• Performance status Eastern Cooperative Oncology Group (ECOG) equal to or less than 2
• Life-expectancy \> 1 year
• Women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study and for a minimum of 6 months after the last dose of doxorubicin
• Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study-specific procedures

You may not qualify if:

• Known congestive heart failure (CHF) (active disease or history of)
• Left ventricular ejection fraction less than 55%
• Planned concurrent administration of other investigational agents
• Planned subsequent therapy with a human epidermal growth factor receptor 2 (HER2)-directed treatments (trastuzumab, pertuzumab, trastuzumab emtansine \[T-DM1\]) or other anthracyclines besides doxorubicin
• Swallowing or absorption problems that might interfere with oral bioavailability of sildenafil
• Known hypersensitivity to doxorubicin, sildenafil or any component of either agent
• Planned chronic nitrate or alpha blocker therapy
• Exclude persons who require ongoing administration of STRONG cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and/or inducers; short periods of exposure to CYP3A4 inhibitors will be allowed (i.e., exposure to aprepitant for three days at the time of doxorubicin exposure)
• Other relative contraindications to sildenafil as defined in the prescribing information:
• Myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months
• Coronary artery disease causing unstable angina
• Resting hypotension (blood pressure \[BP\] \< 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 (AEs)
• Pregnant or nursing

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Related Publications (1)

• Poklepovic A, Qu Y, Dickinson M, Kontos MC, Kmieciak M, Schultz E, Bandopadhyay D, Deng X, Kukreja RC. Randomized study of doxorubicin-based chemotherapy regimens, with and without sildenafil, with analysis of intermediate cardiac markers. Cardiooncology. 2018;4:7. doi: 10.1186/s40959-018-0033-2. Epub 2018 Aug 29.

  PMID: 30221011 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Gastrointestinal Neoplasms; Urogenital Neoplasms; Sarcoma

Interventions

Doxorubicin; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andrew S. Poklepovic, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2011
• First Posted: June 17, 2011
• Study Start: August 11, 2011
• Primary Completion: August 4, 2017
• Study Completion: January 19, 2018
• Last Updated: August 26, 2019

Record last verified: 2019-08

Locations

US (1)