Clinical trial NCT02584309: Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
Official title: A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma, Soft Tissue
Soft Tissue Sarcoma
Undifferentiated Pleomorphic Sarcoma
Leiomyosarcoma
Liposarcoma
Synovial Sarcoma
Myxofibrosarcoma
Angiosarcoma
Fibrosarcoma
Malignant Peripheral Nerve Sheath Tumor
Epithelioid Sarcoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2015-10-22
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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) 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.

Primary outcomes:
measure: Progression-free Survival (PFS) (Arm 1 Only)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Cardiac-related Mortality
timeFrame: Up to 12 months
measure: Percentage of Patients With Heart Failure or Cardiomyopathy
timeFrame: Up to 12 months
measure: Ability of 3D Echocardiogram to Serve as an Early Marker of Cardiac Dysfunction Compared to 2D Echocardiogram Modified Simpson's Biplane Method of LVEF
timeFrame: Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year
measure: Early Detection of Cardiac Dysfunction by 2D Echocardiography Ventricular Strain Compared to 2D Echocardiography Ejection Fraction
timeFrame: Baseline and day 1 of each odd numbered cycle (each cycle is 21 days) up to 1 year
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Brian A Van Tine, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: