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Trial record 34 of 2164 for:    doxorubicin

Doxorubicin With or Without Sildenafil, With Analysis of Cardiac Markers

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ClinicalTrials.gov Identifier: NCT01375699
Recruitment Status : Completed
First Posted : June 17, 2011
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Tracking Information
First Submitted Date  ICMJE June 15, 2011
First Posted Date  ICMJE June 17, 2011
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE August 11, 2011
Actual Primary Completion Date August 4, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Safety of concurrent sildenafil with doxorubicin-based chemotherapy [ Time Frame: 25 months ]
    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.
  • The difference in left ventricular ejection fraction (LVEF) between arms [ Time Frame: 4 years ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 16, 2011)
Safety of concurrent sildenafil with doxorubicin-based chemotherapy [ Time Frame: 25 months ]
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.
Change History Complete list of historical versions of study NCT01375699 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2011)
Comparison of candidate early markers of cardiac injury [ Time Frame: 37 months ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Doxorubicin With or Without Sildenafil, With Analysis of Cardiac Markers
Official Title  ICMJE Randomized Open-label Phase 1b Study of Doxorubicin-based Chemotherapy Regimens, With and Without Sildenafil, With Exploratory Analysis of Intermediate Cardiac Markers
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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Gastrointestinal Cancer
  • Genitourinary Cancer
  • Sarcoma
  • Gynecologic Cancer
Intervention  ICMJE
  • Drug: Doxorubicin
    As prescribed by treating provider.
    Other Names:
    • 123127
    • Doxorubicin Hydrochloride
    • 3-Hydroxyacetyldaunorubicin Hydrochloride
    • Adriamycin Hydrochloride
    • ADM
    • Adriacin
    • Adriamycin
  • Drug: Sildenafil
    Given PO, by mouth
    Other Names:
    • Viagra
    • Revatio
    • Sildenafil Citrate
    • 171599-83-0
Study Arms  ICMJE
  • Experimental: Sildenafil + doxorubicin

    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.

    Interventions:
    • Drug: Doxorubicin
    • Drug: Sildenafil
  • Active Comparator: Doxorubicin-based chemotherapy
    Patients receive doxorubicin hydrochloride IV as clinically indicated and as prescribed by treating provider.
    Intervention: Drug: Doxorubicin
Publications * 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. pii: 7. doi: 10.1186/s40959-018-0033-2. Epub 2018 Aug 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 6, 2015)
26
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2011)
40
Actual Study Completion Date  ICMJE January 19, 2018
Actual Primary Completion Date August 4, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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/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

Exclusion Criteria:

  • 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
  • Known hearing loss
  • History of priapism when exposed to PDE5 inhibitors (sildenafil, vardenafil, tadalafil)
  • Other condition(s) that in the opinion of the investigator might compromise the objectives of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01375699
Other Study ID Numbers  ICMJE MCC-13419
NCI-2011-0098 ( Registry Identifier: CTRP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew S. Poklepovic, MD Massey Cancer Center
PRS Account Virginia Commonwealth University
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP