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Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

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ClinicalTrials.gov Identifier: NCT02584309
Recruitment Status : Recruiting
First Posted : October 22, 2015
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE October 22, 2015
Last Update Posted Date May 17, 2019
Actual Study Start Date  ICMJE February 22, 2016
Estimated Primary Completion Date October 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
Progression-free survival (PFS) (Arm 1 only) [ Time Frame: Up to 5 years ]
  • PFS is defined as the time from randomization to the first occurrence of progression or death, whichever occurs first.
  • If no event exists, the PFS will be censored at the last scheduled disease assessment on study.
  • 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02584309 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
  • Cardiac-related mortality [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0
  • Incidence of heart failure or cardiomyopathy [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0
  • Ability of 3D echocardiogram to serve as an early marker of cardiac dysfunction by measuring echocardiogram parameters of left ventricular ejection fraction by comparing to 2D echocardiogram modified Simpson's biplane method of LVEF [ Time Frame: Day 1 of each odd numbered cycle (estimated median of 4 cycles) ]
    Left ventricular ejection fraction (LVEF) will be evaluated by 2D echocardiogram by modified Simpson's biplane method. Left ventricular systolic function will also be evaluated by 3D echocardiogram.
  • Ability of 3D echocardiogram to serve as an early marker of cardiac dysfunction by measuring echocardiogram parameters of ventricular strain by comparing to 2D echocardiogram modified Simpson's biplane method of LVEF [ Time Frame: Day 1 of each odd numbered cycle (estimated median of 4 cycles) ]
    Left ventricular strain will be evaluated by 2D echocardiogram by evaluating the degree of shortening of the ventricular myocardium. Left ventricular strain will also be evaluated by 3D echocardiogram.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
  • Overall survival (OS) [ Time Frame: Up to 5 years ]
  • Cancer-related mortality [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0
  • Cardiac-related mortality [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0
  • Incidence of heart failure or cardiomyopathy [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0
  • Ability of 3D echocardiogram to serve as an early marker of cardiac dysfunction by measuring echocardiogram parameters of left ventricular ejection fraction by comparing to 2D echocardiogram modified Simpson's biplane method of LVEF [ Time Frame: Day 1 of each odd numbered cycle (estimated median of 4 cycles) ]
    Left ventricular ejection fraction (LVEF) will be evaluated by 2D echocardiogram by modified Simpson's biplane method. Left ventricular systolic function will also be evaluated by 3D echocardiogram.
  • Ability of 3D echocardiogram to serve as an early marker of cardiac dysfunction by measuring echocardiogram parameters of ventricular strain by comparing to 2D echocardiogram modified Simpson's biplane method of LVEF [ Time Frame: Day 1 of each odd numbered cycle (estimated median of 4 cycles) ]
    Left ventricular strain will be evaluated by 2D echocardiogram by evaluating the degree of shortening of the ventricular myocardium. Left ventricular strain will also be evaluated by 3D echocardiogram.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
Official Title  ICMJE A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sarcoma, Soft Tissue
  • Soft Tissue Sarcoma
  • Undifferentiated Pleomorphic Sarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Synovial Sarcoma
  • Myxofibrosarcoma
  • Angiosarcoma
  • Fibrosarcoma
  • Malignant Peripheral Nerve Sheath Tumor
  • Epithelioid Sarcoma
Intervention  ICMJE
  • Drug: Dexrazoxane
    Other Names:
    • Zinecard®
    • Totect®
  • Drug: Doxorubicin
    Other Names:
    • Adriamycin
    • Hydroxydaunomycin Hydrochloride
    • Hydroxydoxorubicin Hydrochloride
    • Rubex
Study Arms  ICMJE
  • Experimental: Arm 1: dexrazoxane & standard of care 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..
    Interventions:
    • Drug: Dexrazoxane
    • Drug: Doxorubicin
  • Active Comparator: Arm 2: control (standard of care doxorubicin)
    • Doxorubicin is given as standard of care. Doxorubicin is typically given at 75 mg/m2 on Day 1 of a 21-day cycle.
    • The last 10 patients enrolled after completion of enrollment to Arm 1 (dexrazoxane & standard of care doxorubicin) will be enrolled to Arm 2 (control arm - standard of care doxorubicin only)
    Intervention: Drug: Doxorubicin
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 20, 2015)
73
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2023
Estimated Primary Completion Date October 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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: Brian A Van Tine, M.D., Ph.D. 314-747-8475 bvantine@wustl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02584309
Other Study ID Numbers  ICMJE 201510049
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.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brian A Van Tine, M.D., Ph.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date May 2019

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