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

A Non-Inferiority Study of Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

Sponsors

Lead Sponsor: Washington University School of Medicine

Source Washington University School of Medicine
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.

Overall Status Recruiting
Start Date February 22, 2016
Completion Date October 31, 2023
Primary Completion Date October 31, 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Progression-free survival (PFS) (Arm 1 only) Up to 5 years
Secondary Outcome
Measure Time Frame
Cardiac-related mortality Up to 5 years
Incidence of heart failure or cardiomyopathy Up to 5 years
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 Day 1 of each odd numbered cycle (estimated median of 4 cycles)
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 Day 1 of each odd numbered cycle (estimated median of 4 cycles)
Enrollment 73
Condition
Intervention

Intervention Type: Drug

Intervention Name: Dexrazoxane

Arm Group Label: Arm 1: dexrazoxane & standard of care doxorubicin

Intervention Type: Drug

Intervention Name: Doxorubicin

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Brian A Van Tine, M.D., Ph.D. Principal Investigator Washington University School of Medicine
Overall Contact

Last Name: Brian A Van Tine, M.D., Ph.D.

Phone: 314-747-8475

Email: [email protected]

Location
Facility: Status: Contact: Investigator: Washington University School of Medicine Brian A Van Tine, M.D., Ph.D. 314-747-8475 [email protected] Brian A Van Tine, M.D., Ph.D. Principal 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. Sub-Investigator Daniel Lenihan, M.D. Sub-Investigator Jose Alvarez-Cardona, M.D. Sub-Investigator John Gorcsan, M.D. Sub-Investigator Joshua Mitchell, M.D. Sub-Investigator Kathleen Zhang, M.D. Sub-Investigator
Location Countries

United States

Verification Date

March 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm 1: dexrazoxane & standard of care doxorubicin

Type: Experimental

Description: 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..

Label: Arm 2: control (standard of care doxorubicin)

Type: Active Comparator

Description: 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)

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov