NCT02584309CompletedPhase 2
A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
Washington University School of Medicine1 site in 1 country73 target enrollmentStarted: February 22, 2016Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- Progression-free Survival (PFS) (Arm 1 Only)
Study Overview
Brief 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 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
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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).
Exclusion Criteria
- •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).
- •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.
Arms & Interventions
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..
Intervention: Dexrazoxane (Drug)
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..
Intervention: Doxorubicin (Drug)
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.
Intervention: Dexrazoxane (Drug)
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.
Intervention: Doxorubicin (Drug)
Outcomes
Primary Outcomes
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).
Secondary Outcomes
- Cardiac-related Mortality(Up to 12 months)
- Percentage of Patients With Heart Failure or Cardiomyopathy(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(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(Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year)
Investigators
Study Sites (1)
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