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Trial record 30 of 65 for:    Sarcoma | "Dermatofibroma"

Doxorubicin With Upfront Dexrazoxane Plus Olaratumab 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 : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The purpose of this research study is to look at whether giving a drug called dexrazoxane plus olaratumab 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).

Condition or disease Intervention/treatment Phase
Sarcoma, Soft Tissue Soft Tissue Sarcoma Undifferentiated Pleomorphic Sarcoma Leiomyosarcoma Liposarcoma Synovial Sarcoma Myxofibrosarcoma Angiosarcoma Fibrosarcoma Malignant Peripheral Nerve Sheath Tumor Epithelioid Sarcoma Drug: Dexrazoxane Drug: Doxorubicin Drug: Olaratumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 73 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
Actual Study Start Date : February 22, 2016
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : October 31, 2023


Arm Intervention/treatment
Experimental: Arm 1: dexrazoxane & standard of care doxorubicin + olaratumab
  • Dexrazoxane will be given intravenously on an outpatie2. -nt 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.
  • Olaratumab is typically given on Days 1 and 8 of 21-day cycle at a dose of 15 mg/kg. Both doxorubicin and olaratumab are being given as routine care; their administration is not dictated per protocol.
  • In the event of a national shortage of dexrazoxane, 72-hour infusional doxorubicin can be used instead of dexrazoxane and bolus doxorubicin..
Drug: Dexrazoxane
Other Names:
  • Zinecard®
  • Totect®

Drug: Doxorubicin
Other Names:
  • Adriamycin
  • Hydroxydaunomycin Hydrochloride
  • Hydroxydoxorubicin Hydrochloride
  • Rubex

Drug: Olaratumab
Other Name: Lartruvo

Active Comparator: Arm 2: control (standard of care doxorubicin + olaratumab)
  • Doxorubicin is given as standard of care. Doxorubicin is typically given at 75 mg/m2 on Day 1 of a 21-day cycle.

    --Olaratumab is typically given on Days 1 and 8 of 21-day cycle at a dose of 15 mg/kg. Both doxorubicin and olaratumab are being given as routine care; their administration is not dictated per protocol.

  • 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)
Drug: Doxorubicin
Other Names:
  • Adriamycin
  • Hydroxydaunomycin Hydrochloride
  • Hydroxydoxorubicin Hydrochloride
  • Rubex

Drug: Olaratumab
Other Name: Lartruvo




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Cardiac-related mortality [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0

  2. Incidence of heart failure or cardiomyopathy [ Time Frame: Up to 5 years ]
    Measured using CTCAE Version 4.0

  3. 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.

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) and olaratumab (starting dose of 15 mg/kg) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02584309


Contacts
Contact: Brian A Van Tine, M.D., Ph.D. 314-747-8475 bvantine@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Brian A Van Tine, M.D., Ph.D.    314-747-8475    bvantine@wustl.edu   
Principal Investigator: Brian A Van Tine, M.D., Ph.D.         
Sub-Investigator: Ashley E Frith, M.D.         
Sub-Investigator: Douglas R Adkins, M.D.         
Sub-Investigator: Ronald J Krone, M.D.         
Sub-Investigator: Justin Vader, M.D.         
Sub-Investigator: George Heberton, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Angela Hirbe, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Brian A Van Tine, M.D., Ph.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02584309     History of Changes
Other Study ID Numbers: 201510049
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Synovial
Histiocytoma, Malignant Fibrous
Histiocytoma
Leiomyosarcoma
Liposarcoma
Hemangiosarcoma
Fibrosarcoma
Nerve Sheath Neoplasms
Neurilemmoma
Neurofibrosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Adipose Tissue
Neoplasms, Connective Tissue
Neoplasms, Vascular Tissue
Neoplasms, Fibrous Tissue
Neoplasms, Nerve Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Neurofibroma