Sarcoma, Soft TissuePhase 2NCT02584309
Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
A Phase 2 study testing Dexrazoxane and Doxorubicin in people with Sarcoma, Soft Tissue and Soft Tissue Sarcoma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this research study is to look at whether giving a drug called dexrazoxane with standard of care doxorubicin affects the progression of the disease. Dexrazoxane is often given at the same time as doxorubicin to help reduce the incidence and severity of disease of the heart muscle (which can be caused by… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma, Soft Tissue, Soft Tissue Sarcoma, Undifferentiated Pleomorphic Sarcoma
- What is being tested?
- Dexrazoxane and Doxorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2016to 17 Jul 2022
- 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
- Histologically confirmed grade 2 or 3 soft tissue sarcoma that is unresectable or metastatic. Surgery for primary or metastatic disease after chemotherapy following a response is allowed. Patients with the following tumor types are eligible:
- Undifferentiated pleomorphic sarcoma
- Leiomyosarcoma
- Malignant fibrous histiocytoma
- Liposarcoma (myxoid/round cell, pleomorphic or dedifferentiated)
- Synovial sarcoma
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- Myxofibrosarcoma
- Angiosarcoma
- Fibrosarcoma
- Malignant peripheral nerve sheath tumor
- Epithelioid sarcoma
- Unclassified high-grade sarcoma (not otherwise specified)
- Soft tissue sarcoma for which treatment with an anthracycline is appropriate at the approval of the Principal Investigator (PI)
- Measurable disease according to RECIST 1.1; that is, measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Planning to initiate treatment with doxorubicin (starting dose 75 mg/m2) as routine care.
- Prior adjuvant chemotherapy with gemcitabine and/or docetaxel/paclitaxel is allowed.
- At least 18 years of age.
- ECOG performance status of 0 or 1
- Adequate organ function defined as:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR Creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. Creatinine clearance should be calculated using the actual weight from day 1 of cycle
- Women of childbearing 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 must inform her treating physician immediately.
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- Myocardial infarction within the past 12 months, or stable or unstable angina.
- Systolic heart failure defined as left ventricular ejection fraction ≤ 45%.
- Symptomatic valvular heart disease.
- Prior chemotherapy for advanced or metastatic disease.
- Known brain metastases.
- Prior or second primary malignancies within the last two years (except carcinoma in situ of the cervix, non-metastatic prostate cancer, or basal cell or squamous cell carcinoma of the skin which were treated with local resection only; prior adjuvant androgen deprivation therapy in the case of prostate cancer is permitted, but current adjuvant androgen deprivation therapy is not).
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- Currently receiving any investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dexrazoxane or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with dexrazoxane. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Prior treatment with anthracyclines.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
The purpose of this research study is to look at whether giving a drug called dexrazoxane with standard of care doxorubicin affects the progression of the disease. Dexrazoxane is often given at the same time as doxorubicin to help reduce the incidence and severity of disease of the heart muscle (which can be caused by doxorubicin).
In January 2019 Eli Lilly and Company reported that the results of the Phase 3 study of olaratumab (Lartruvo), in combination with doxorubicin in patients with advanced or metastatic soft tissue sarcoma, did not confirm the clinical benefit of olaratumab in combination with doxorubicin as compared to doxorubicin alone. Therefore olaratumab is being removed from the front line standard of care regimen. Amendment #9 was made to the protocol to reflect these changes to the standard of care treatment.
- Conditions
- Sarcoma, Soft Tissue, Soft Tissue Sarcoma, Undifferentiated Pleomorphic Sarcoma, Leiomyosarcoma, Liposarcoma, Synovial Sarcoma
- Being tested
- Dexrazoxane, Doxorubicin
- Medical subject headings
- Sarcoma, Histiocytoma, Malignant Fibrous, Leiomyosarcoma, Liposarcoma, Sarcoma, Synovial, Dermatofibrosarcoma, Hemangiosarcoma, Fibrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexrazoxaneDrug
Also called Zinecard®, Totect®
DoxorubicinDrug
Also called Adriamycin, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin Hydrochloride, Rubex
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Doxorubicin and Upfront Dexrazoxane | Experimental | * Dexrazoxane will be given intravenously on an outpatient basis over 15 minutes on each day that doxorubicin is given.
* Dexrazoxane should be given no more than 30 minutes prior to administration of doxorubicin, which is typically given on Day 1 of a 21-day cycle.
* Dosing is a 10:1 ratio of dexrazoxane to doxorubicin; doxorubicin is typically given at 75 mg/m2, so dexrazoxane dosing would be 750 mg/m2.
* In the event of a national shortage of dexrazoxane, 72-hour infusional doxorubicin can be used instead of dexrazoxane and bolus doxorubicin.. Receives: Drug: Dexrazoxane; Drug: Doxorubicin |
| Arm 2: control (Doxorubicin and Standard of Care Dexrazoxane) | Active comparator | * Doxorubicin is given as standard of care. Doxorubicin is typically given at 75 mg/m2 on Day 1 of a 21-day cycle.
* Starting with cycle 5, standard of care dexrazoxane (75 mg/m2) will be given for 4 cycles.
* The last 10 patients enrolled after completion of enrollment to Arm 1 will be enrolled to Arm 2. Receives: Drug: Dexrazoxane; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) (Arm 1 Only)
- PFS is defined as the time from on study to the first occurrence of progression or death, whichever occurs first.
- If no event exists, the PFS will be censored at the last follow-up.
- Progressive disease - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measured: Up to 5 years
Secondary outcomes (4)
Cardiac-related Mortality
Death due to cardiovascular while on study (heart failure, myocardial infarction, fatal arrhythmia).
Measured: Up to 12 months
Percentage of Patients With Heart Failure or Cardiomyopathy
- Cardiomyopathy is now referred to as cancer therapy related cardiac dysfunction (CTRCD) by the recent consensus statement of the International Cardio-Oncology Society. Moderate CTRCD is defined as >10% ejection fraction drop to <50%. Mild CTRCD is defined as drop in ≥15% ventricular strain or if no ventricular strain, a drop in ejection fraction of ≥50%.
- Heart failure is defined according to the recent Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.
Measured: Up to 12 months
Ability of 3D Echocardiogram to Serve as an Early Marker of Cardiac Dysfunction Compared to 2D Echocardiogram Modified Simpson's Biplane Method of LVEF
- Cardiac dysfunction for this outcome measure is defined as moderate cancer therapy related cardiac dysfunction (CTRCD) as assessed by 2D Echocardiogram Modified Simpson's Biplane Method of LVEF. Moderate CTRCD is defined as >10% ejection fraction drop to <50%.
- 3D echocardiograms were reviewed for evidence of cardiac dysfunction prior to onset of Moderate CTRCD by 2D echocardiogram. Dysfunction on 3D Echo was defined as >10% ejection fraction drop to <50%.
Measured: Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year
Early Detection of Cardiac Dysfunction by 2D Echocardiography Ventricular Strain Compared to 2D Echocardiography Ejection Fraction
- Cardiac dysfunction for this outcome measure is defined as moderate cancer therapy related cardiac dysfunction (CTRCD) by 2D Echocardiogram Modified Simpson's Biplane Method of LVEF. Moderate CTRCD is defined as >10% ejection fraction drop to <50%.
- Patients were assessed for early evidence of dysfunction by strain defined as a relative drop in global longitudinal strain (GLS) by 15% and GLS > -17%.
Measured: Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study start22 Feb 2016
- Primary completion17 Jul 2022
- Study completion17 Jul 2022
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.
- Other trials for Sarcoma, Soft TissueStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brian A Van Tine, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02584309
- Sponsor's protocol ID
- 201510049
- Status last verified
- Oct 2023
- First submitted
- 12 Oct 2015
- Last updated
- 7 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
- ClinicalTrials.gov ID
- NCT02584309
- Acronym / sponsor ID
- 201510049
- Conditions
- Sarcoma, Soft Tissue, Soft Tissue Sarcoma, Undifferentiated Pleomorphic Sarcoma, Leiomyosarcoma, Liposarcoma, Synovial Sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 22 Feb 2016 (actual)
- Primary completion
- 17 Jul 2022 (actual)
- Study completion
- 17 Jul 2022 (actual)
- First posted
- 22 Oct 2015 (estimated)
- Results
- Posted 7 Nov 2023
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 research study is to look at whether giving a drug called dexrazoxane with standard of care doxorubicin affects the progression of the disease. Dexrazoxane is often given at the same time as doxorubicin to help reduce the incidence and severity of disease of the heart muscle (which can be caused by doxorubicin).
In January 2019 Eli Lilly and Company reported that the results of the Phase 3 study of olaratumab (Lartruvo), in combination with doxorubicin in patients with advanced or metastatic soft tissue sarcoma, did not confirm the clinical benefit of olaratumab in combination with doxorubicin as compared to doxorubicin alone. Therefore olaratumab is being removed from the front line standard of care regimen. Amendment #9 was made to the protocol to reflect these changes to the standard of care treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Doxorubicin and Upfront Dexrazoxane | Experimental | Drug: Dexrazoxane, Drug: Doxorubicin* Dexrazoxane will be given intravenously on an outpatient basis over 15 minutes on each day that doxorubicin is given. * Dexrazoxane should be given no more than 30 minutes prior to administration of doxorubicin, which is typically given on Day 1 of a 21-day cycle. * Dosing is a 10:1 ratio of dexrazoxane to doxorubicin; doxorubicin is typically given at 75 mg/m2, so dexrazoxane dosing would be 750 mg/m2. * In the event of a national shortage of dexrazoxane, 72-hour infusional doxorubicin can be used instead of dexrazoxane and bolus doxorubicin.. |
| Arm 2: control (Doxorubicin and Standard of Care Dexrazoxane) | Active comparator | Drug: Dexrazoxane, Drug: Doxorubicin* Doxorubicin is given as standard of care. Doxorubicin is typically given at 75 mg/m2 on Day 1 of a 21-day cycle. * Starting with cycle 5, standard of care dexrazoxane (75 mg/m2) will be given for 4 cycles. * The last 10 patients enrolled after completion of enrollment to Arm 1 will be enrolled to Arm 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Histologically confirmed grade 2 or 3 soft tissue sarcoma that is unresectable or metastatic. Surgery for primary or metastatic disease after chemotherapy following a response is allowed. Patients with the following tumor types are eligible:
- Measurable disease according to RECIST 1.1; that is, measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Planning to initiate treatment with doxorubicin (starting dose 75 mg/m2) as routine care.
- Prior adjuvant chemotherapy with gemcitabine and/or docetaxel/paclitaxel is allowed.
- At least 18 years of age.
Key exclusion criteria (12 listed)
- Myocardial infarction within the past 12 months, or stable or unstable angina.
- Systolic heart failure defined as left ventricular ejection fraction ≤ 45%.
- Symptomatic valvular heart disease.
- Prior chemotherapy for advanced or metastatic disease.
- Known brain metastases.
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 |
|---|---|---|
| DexrazoxaneAlso: Zinecard®, Totect® | Drug | Arm 1: Doxorubicin and Upfront Dexrazoxane, Arm 2: control (Doxorubicin and Standard of Care Dexrazoxane) |
| DoxorubicinAlso: Adriamycin, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin Hydrochloride, Rubex | Drug | Arm 1: Doxorubicin and Upfront Dexrazoxane, Arm 2: control (Doxorubicin and Standard of Care Dexrazoxane) |
Primary outcome
Progression-free Survival (PFS) (Arm 1 Only)
Time frame: Up to 5 years
* PFS is defined as the time from on study to the first occurrence of progression or death, whichever occurs first. * If no event exists, the PFS will be censored at the last follow-up. * Progressive disease - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
4 secondary outcomes
Cardiac-related Mortality
Time frame: Up to 12 months
Percentage of Patients With Heart Failure or Cardiomyopathy
Time frame: Up to 12 months
Ability of 3D Echocardiogram to Serve as an Early Marker of Cardiac Dysfunction Compared to 2D Echocardiogram Modified Simpson's Biplane Method of LVEF
Time frame: Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year
Early Detection of Cardiac Dysfunction by 2D Echocardiography Ventricular Strain Compared to 2D Echocardiography Ejection Fraction
Time frame: Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Brian A Van Tine, M.D., Ph.D. principal investigator
Washington University School of Medicine
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 Dexrazoxane and Doxorubicin in people with Sarcoma, Soft Tissue and Soft Tissue Sarcoma, run by Washington University School of Medicine 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 27 inclusion and 12 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 7 Nov 2023. 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 7 Nov 2023). 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?
Progression-free Survival (PFS) (Arm 1 Only) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Nov 2023.