Breast CancerPhase 1NCT01375699
Doxorubicin With or Without Sildenafil, With Analysis of Cardiac Markers
A Phase 1 study testing Doxorubicin and Sildenafil in people with Breast Cancer and Gastrointestinal Cancer, run by Virginia Commonwealth University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Gastrointestinal Cancer, Genitourinary Cancer
- What is being tested?
- Doxorubicin and Sildenafil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2011to 19 Jan 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298-0037
About this study
Official title: Randomized Open-label Phase 1b Study of Doxorubicin-based Chemotherapy Regimens, With and Without Sildenafil, With Exploratory Analysis of Intermediate 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.
Read the 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.
- Being tested
- Doxorubicin, Sildenafil
- Keywords
- Breast cancer, Gastrointestinal cancer, Genitourinary cancer, Sarcoma, Gynecologic cancer
- Medical subject headings
- Breast Neoplasms, Gastrointestinal Neoplasms, Urogenital Neoplasms, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Also called 123127, Doxorubicin Hydrochloride, 3-Hydroxyacetyldaunorubicin Hydrochloride, Adriamycin Hydrochloride
As prescribed by treating provider.
SildenafilDrug
Also called Viagra, Revatio, Sildenafil Citrate, 171599-83-0
Given PO, by mouth
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Doxorubicin; Drug: Sildenafil |
| Doxorubicin-based chemotherapy | Active comparator | Patients receive doxorubicin hydrochloride IV as clinically indicated and as prescribed by treating provider. Receives: Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 4 years
Secondary outcomes (1)
Comparison of candidate early markers of cardiac injury
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.
Measured: 37 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2011 (estimated)
- Study start11 Aug 2011
- Primary completion4 Aug 2017
- Study completion19 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew S. Poklepovic, MD, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01375699
- Sponsor's protocol ID
- MCC-13419
- Other IDs
- NCI-2011-0098
- Status last verified
- Aug 2019
- First submitted
- 15 Jun 2011
- Last updated
- 26 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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;4:7. doi: 10.1186/s40959-018-0033-2. Epub 2018 Aug 29.
PubMed 30221011
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Open-label Phase 1b Study of Doxorubicin-based Chemotherapy Regimens, With and Without Sildenafil, With Exploratory Analysis of Intermediate Cardiac Markers
- ClinicalTrials.gov ID
- NCT01375699
- Acronym / sponsor ID
- MCC-13419
- Keywords
- Breast cancer, Gastrointestinal cancer, Genitourinary cancer, Sarcoma, Gynecologic cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- 11 Aug 2011 (actual)
- Primary completion
- 4 Aug 2017 (actual)
- Study completion
- 19 Jan 2018 (actual)
- First posted
- 17 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil + doxorubicin | Experimental | Drug: Doxorubicin, Drug: SildenafilPatients 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. |
| Doxorubicin-based chemotherapy | Active comparator | Drug: DoxorubicinPatients receive doxorubicin hydrochloride IV as clinically indicated and as prescribed by treating provider. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxorubicinAlso: 123127, Doxorubicin Hydrochloride, 3-Hydroxyacetyldaunorubicin Hydrochloride, Adriamycin HydrochlorideAs prescribed by treating provider. | Drug | Doxorubicin-based chemotherapy, Sildenafil + doxorubicin |
| SildenafilAlso: Viagra, Revatio, Sildenafil Citrate, 171599-83-0Given PO, by mouth | Drug | Sildenafil + doxorubicin |
Primary outcome
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.
1 secondary outcome
Comparison of candidate early markers of cardiac injury
Time frame: 37 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2019.
- Results publication: PubMed 30221011Poklepovic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew S. Poklepovic, MD principal investigator
Massey Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Doxorubicin and Sildenafil in people with Breast Cancer and Gastrointestinal Cancer, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of concurrent sildenafil with doxorubicin-based chemotherapy (time frame: 25 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01375699, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2019.