Breast CancerPhase 2NCT01205503
Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and Tumor Necrosis Factor Alpha (TNF-α) Release
A Phase 2 study testing Mesna, Saline and Doxorubicin in people with Breast Cancer and Non-Hodgkin's Lymphoma, run by Mara Chambers at 1 site in United States.
Trial summary
The purpose of this study is to determine whether the drug mesna is able to block a series of chemical changes that occur in the blood of patients who receive the chemotherapy medicine doxorubicin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Non-Hodgkin's Lymphoma
- What is being tested?
- Mesna, Saline and Doxorubicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Apr 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Participants must have histologically or cytologically confirmed breast cancer or non-hodgkin lymphoma and independent of protocol eligibility be determined to require one of the chemotherapy regimens listed below
- Participants must require as standard-of-care treatment a chemotherapy regimen that includes one of the following combinations:
- doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2;
- doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, and docetaxel 75 mg/m2;
- doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (capped at 2 mg dose), and prednisone 100 mg +/- rituximab 375 mg/m2
- Age >18 years.Because these treatment regimens are rarely used in pediatric oncology, children are excluded from this study but will be eligible for future pediatric phase 2 trials.
Show all 19Show fewer
- Life expectancy of greater than 6 months.
- Zubrod performance score 2 or better.
- Patients must have normal organ and marrow function as defined below:
- leukocytes >3,000/microliter (mcL) (unless due to cancer in marrow)
- absolute neutrophil count >1,500/mcL (unless due to cancer in marrow)
- platelets >100,000/mcL (unless due to cancer in marrow)
- total bilirubin <1.5 X normal institutional limits
- Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT) <2.5 X institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- left ventricular function ≥ 50 % ejection fraction
- Because the standard of care chemotherapy agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial because progressive neurologic dysfunction would confound the evaluation of neuro-cognitive outcomes.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to mesna or other agents used in the study (ie. sulfur containing drugs including "sulfa antibiotics" and celecoxib).
- Patients requiring ongoing pharmacologic treatment of dementia are excluded.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because the chemotherapy agents have known teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy.
- HIV-positivity is NOT a specific exclusion criteria.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
About this study
Official title: Randomized, Blinded Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and TNF-α Release
The purpose of this study is to determine whether the drug mesna is able to block a series of chemical changes that occur in the blood of patients who receive the chemotherapy medicine doxorubicin. The researchers believe these blood chemical changes may the cause of "cloudy thinking" or "chemobrain" that are reported by some patients receiving chemotherapy.
Read the detailed description
Patients with lymphoma and breast cancer receiving chemotherapy regimens that include anthracycline drugs, such as doxorubicin, are at risk for developing cognitive and cardiac impairment. This potential cognitive impairment is refered to as "chemobrain" by some patients. We have demonstrated in mice that the drug mesna, which is used to prevent other complications of other chemotherapy drugs, prevents certain types of doxorubicin-induced damage of blood proteins. Blocking doxorubicin's damage of these blood proteins has blunted or prevented the subsequent markers of neurologic and cardiac injury in mice. This clinical trial will determine if mesna prevents doxorubicin-induced damage of blood proteins in cancer patients, and may establish if blood protein injury is the first step in anthracycline-induced cognitive and cardiac dysfunction and if using the drug mesna can blunt or prevent these changes in blood markers of injury for patients with cancer.
- Conditions
- Breast Cancer, Non-Hodgkin's Lymphoma
- Being tested
- Mesna, Saline, Doxorubicin, Cyclophosphamide
- Keywords
- chemobrain, Oxidative Stress, Mesna
- Medical subject headings
- Breast Neoplasms, Lymphoma, Non-Hodgkin, Chemotherapy-Related Cognitive Impairment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesnaDrug
Also called Mesnex
Mesna: 360 mg/m2 in 50 mL normal saline (NS) either on cycle 2 or cycle 1, day 1. Infused over 15 minutes
SalineDrug
Also called Placebo
Saline (used as a placebo) infused over the same time as mesna intervention
DoxorubicinDrug
Also called Adriamycin
60mg/m2 given IV over 15 minutes after receiving mesna or saline. Can allow for premedications of Ondansetron 8 mg orally, dexamethasone 12 mg orally, Aprepitant 125 mg orally.
CyclophosphamideDrug
Also called Endoxan, Cytoxan, Neosar, Procytox
600 mg/m2 IV over 30 minutes. Start 6 hours after doxorubicin started.
| Study group | Role | What they receive |
|---|---|---|
| Cycle 1 Saline; Cycle 2 Mesna | Other | Saline infused over 15 minutes administered prior to and 3 hours post doxorubicin infusion (over 15 minutes) with following Cyclophosphamide 6 hours post doxorubicin during 1st cycle, then Mesna administered (infused over 15 minutes, 360 mg/m2) prior to and 3 hours post doxorubicin infusion with following Cyclophosphamide 6 hours post doxorubicin during 2nd cycle Receives: Drug: Mesna; Drug: Saline; Drug: Doxorubicin; Drug: Cyclophosphamide |
| Cycle 1 Mesna; Cycle 2 Saline | Other | Mesna administered (infused over 15 minutes, 360 mg/m2) prior to and 3 hours post doxorubicin infusion with following Cyclophosphamide 6 hours post doxorubicin during 1st cycle, then Saline administered prior to and 3 hours post doxorubicin infusion (over 15 minutes) with following Cyclophosphamide 6 hours post doxorubicin during 2nd cycle Receives: Drug: Mesna; Drug: Saline; Drug: Doxorubicin; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
TNF-alpha Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of TNF-alpha at the 4 time points outlined in the protocol for each group.
Measured: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Secondary outcomes (4)
Protein Carbonyl Percent Changes From Baseline in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of percent changes from baseline of Protein Carbonyl at the 4 time points outlined in the protocol for each group. All measurements after naive baseline were adjusted as percent change from each individual's baseline measure.
Measured: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Plasma HNE Percent Changes From Baseline in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of the percent change from baseline of Plasma HNE at the 4 time points outlined in the protocol for each group. All measurements after naive baseline were adjusted as percent change from each individual's baseline measure.
Measured: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Troponin Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of troponin at the 4 time points outlined in the protocol for each group.
Measured: prior to and 3 hours post doxorubicin and between cycles 1 and 2
B-type Natriuretic Peptide (BNP) Blood Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of BNP at the 4 time points outlined in protocol for each of the groups. This is a 32-amino acid polypeptide secreted by heart ventricles in response to excessive stretching of cardiomyocytes.
Measured: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionAug 2012
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mara Chambers
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mara Chambers, University of Kentucky
- Investigators
- Mara Chambers, M.D., Principal investigator, Markey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01205503
- Sponsor's protocol ID
- 10-0431-F1V
- Status last verified
- Jan 2016
- First submitted
- 17 Sep 2010
- Last updated
- 24 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The de-identified data is already available as part of the published article supplement. PubMed Identification (ID) # 25909710
Publications
Hayslip J, Dressler EV, Weiss H, Taylor TJ, Chambers M, Noel T, Miriyala S, Keeney JT, Ren X, Sultana R, Vore M, Butterfield DA, St Clair D, Moscow JA. Plasma TNF-alpha and Soluble TNF Receptor Levels after Doxorubicin with or without Co-Administration of Mesna-A Randomized, Cross-Over Clinical Study. PLoS One. 2015 Apr 24;10(4):e0124988. doi: 10.1371/journal.pone.0124988. eCollection 2015.
PubMed 25909710
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Blinded Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and TNF-α Release
- ClinicalTrials.gov ID
- NCT01205503
- Acronym / sponsor ID
- 10-0431-F1V
- Conditions
- Breast Cancer, Non-Hodgkin's Lymphoma
- Keywords
- chemobrain, Oxidative Stress, Mesna
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Mara ChambersUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 20 Sep 2010 (estimated)
- Results
- Posted 24 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the drug mesna is able to block a series of chemical changes that occur in the blood of patients who receive the chemotherapy medicine doxorubicin. The researchers believe these blood chemical changes may the cause of "cloudy thinking" or "chemobrain" that are reported by some patients receiving chemotherapy.
Detailed description
Patients with lymphoma and breast cancer receiving chemotherapy regimens that include anthracycline drugs, such as doxorubicin, are at risk for developing cognitive and cardiac impairment. This potential cognitive impairment is refered to as "chemobrain" by some patients. We have demonstrated in mice that the drug mesna, which is used to prevent other complications of other chemotherapy drugs, prevents certain types of doxorubicin-induced damage of blood proteins. Blocking doxorubicin's damage of these blood proteins has blunted or prevented the subsequent markers of neurologic and cardiac injury in mice. This clinical trial will determine if mesna prevents doxorubicin-induced damage of blood proteins in cancer patients, and may establish if blood protein injury is the first step in anthracycline-induced cognitive and cardiac dysfunction and if using the drug mesna can blunt or prevent these changes in blood markers of injury for patients with cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cycle 1 Saline; Cycle 2 Mesna | Other | Drug: Mesna, Drug: Saline, Drug: Doxorubicin, Drug: CyclophosphamideSaline infused over 15 minutes administered prior to and 3 hours post doxorubicin infusion (over 15 minutes) with following Cyclophosphamide 6 hours post doxorubicin during 1st cycle, then Mesna administered (infused over 15 minutes, 360 mg/m2) prior to and 3 hours post doxorubicin infusion with following Cyclophosphamide 6 hours post doxorubicin during 2nd cycle |
| Cycle 1 Mesna; Cycle 2 Saline | Other | Drug: Mesna, Drug: Saline, Drug: Doxorubicin, Drug: CyclophosphamideMesna administered (infused over 15 minutes, 360 mg/m2) prior to and 3 hours post doxorubicin infusion with following Cyclophosphamide 6 hours post doxorubicin during 1st cycle, then Saline administered prior to and 3 hours post doxorubicin infusion (over 15 minutes) with following Cyclophosphamide 6 hours post doxorubicin during 2nd cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must have histologically or cytologically confirmed breast cancer or non-hodgkin lymphoma and independent of protocol eligibility be determined to require one of the chemotherapy regimens listed below
- Participants must require as standard-of-care treatment a chemotherapy regimen that includes one of the following combinations:
- doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2;
- doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, and docetaxel 75 mg/m2;
- doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (capped at 2 mg dose), and prednisone 100 mg +/- rituximab 375 mg/m2
Key exclusion criteria (8 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial because progressive neurologic dysfunction would confound the evaluation of neuro-cognitive outcomes.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to mesna or other agents used in the study (ie. sulfur containing drugs including "sulfa antibiotics" and celecoxib).
- Patients requiring ongoing pharmacologic treatment of dementia are excluded.
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 |
|---|---|---|
| MesnaAlso: MesnexMesna: 360 mg/m2 in 50 mL normal saline (NS) either on cycle 2 or cycle 1, day 1. Infused over 15 minutes | Drug | Cycle 1 Mesna; Cycle 2 Saline, Cycle 1 Saline; Cycle 2 Mesna |
| SalineAlso: PlaceboSaline (used as a placebo) infused over the same time as mesna intervention | Drug | Cycle 1 Mesna; Cycle 2 Saline, Cycle 1 Saline; Cycle 2 Mesna |
| DoxorubicinAlso: Adriamycin60mg/m2 given IV over 15 minutes after receiving mesna or saline. Can allow for premedications of Ondansetron 8 mg orally, dexamethasone 12 mg orally, Aprepitant 125 mg orally. | Drug | Cycle 1 Mesna; Cycle 2 Saline, Cycle 1 Saline; Cycle 2 Mesna |
| CyclophosphamideAlso: Endoxan, Cytoxan, Neosar, Procytox600 mg/m2 IV over 30 minutes. Start 6 hours after doxorubicin started. | Drug | Cycle 1 Mesna; Cycle 2 Saline, Cycle 1 Saline; Cycle 2 Mesna |
Primary outcome
TNF-alpha Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Continuous Measure of TNF-alpha at the 4 time points outlined in the protocol for each group.
4 secondary outcomes
Protein Carbonyl Percent Changes From Baseline in Patients Receiving Doxorubicin Containing Chemotherapy
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Plasma HNE Percent Changes From Baseline in Patients Receiving Doxorubicin Containing Chemotherapy
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Troponin Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
B-type Natriuretic Peptide (BNP) Blood Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25909710Hayslip J, Dressler EV, Weiss H, Taylor TJ, Chambers M, Noel T, Miriyala S, Keeney JT, Ren X, Sultana R, Vore M, Butterfield DA, St Clair D, Moscow JA. Plasma TNF-alpha and Soluble TNF Receptor Levels after Doxorubicin with or without Co-Administration of Mesna-A Randomized, Cross-Over Clinical Study. PLoS One. 2015 Apr 24;10(4):e0124988. doi: 10.1371/journal.pone.0124988. eCollection 2015.
- Individual participant dataSharing planned: Yes. The de-identified data is already available as part of the published article supplement. PubMed Identification (ID) # 25909710
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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.
Mara Chambers, M.D. principal investigator
Markey 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 2 study testing Mesna, Saline and Doxorubicin in people with Breast Cancer and Non-Hodgkin's Lymphoma, run by Mara Chambers 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 19 inclusion and 8 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 24 Feb 2016. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
TNF-alpha Levels in Patients Receiving Doxorubicin Containing Chemotherapy (time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2). 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 NCT01205503, 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 24 Feb 2016.