Amrubicin Chemotherapy as First Line in Metastatic or Unresectable Soft Tissue Sarcoma (ARSARC-PI-0010)

A Phase II Study of Amrubicin Chemotherapy as First Line Treatment in Patients With Metastatic or Unresectable Soft Tissue Sarcoma

Primary Objectives

1. To evaluate the Response Rate (RR) for amrubicin in patients with metastatic or advanced sarcoma as first line therapy.
2. To evaluate Progression Free Survival (PFS).

Secondary Objectives

1. To assess the safety and tolerability of amrubicin in this patient population.
2. To evaluate whether certain histologic subtypes of sarcoma demonstrate a differential response to amrubicin.
3. To investigate quality of response with radiographic evaluation using both Response Evaluation Criteria In Solid Tumors (RECIST) and Choi criteria.
4. To evaluate overall survival (OS).

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Amrubicin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Santa Monica
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (age 18 years or older)
• Pathological diagnosis of soft tissue sarcoma. Pathology materials must be submitted and reviewed.
• Patients must have unresectable locally advanced or metastatic progressive disease prior to enrollment. Disease extent must be determined by scans (CT or PET CT) within 6 weeks of enrollment.
• No prior chemotherapy for soft tissue sarcoma.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function including the following:
• Adequate bone marrow reserve: absolute neutrophil count (segmented and bands) (ANC) 1.5 x 109/L, platelet count 100 x 109/L, and hemoglobin 90 g/L,
• Hepatic: bilirubin 1.5 x the upper limit of normal (ULN), ALT and AST 3.0 x ULN,
• Renal: serum creatinine 1.5 x ULN or calculated creatinine clearance greater than 60 mL/min,
• Cardiac: Left ventricular ejection fraction (LVEF) 50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA);
• All labs must be done within 2 weeks prior to enrollment.
• Negative serum pregnancy test at the time of enrollment for females of childbearing potential;
• For males and females of child-producing potential, use of effective contraceptive methods during the study;
• Ability to understand the requirements of the study and provide written informed consent.

Exclusion Criteria:

• Pregnant or nursing females
• Chest radiotherapy with curative intent to the primary disease complex less than or equal to 28 days prior to first dose; cranial radiotherapy less than or equal to 21 days prior to first dose; radiotherapy to all other areas less than or equal to 7 days prior to first dose
• Concurrent severe or uncontrolled medical disease (eg, active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, active viral hepatitis or chronic liver disease) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study
• Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable for 2 weeks after radiotherapy; if the patient is on corticosteroids, the dose of corticosteroids must have been stable for 2 weeks prior to first dose of study treatment, or be in the process of being tapered
• Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis.
• Patients with known history of seropositive human immunodeficiency virus (HIV) or patients who are receiving immunosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications. HIV testing is not required for inclusion in the trial.
• Known hypersensitivity to any of the components of the i.v. formulation of amrubicin.
• Psychiatric disorder or any other personal circumstances that prevent compliance with the study protocol.
• Inability or unwillingness to comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: All patients; All participants who received Amrubicin.	Drug: Amrubicin; Synthetic 9-aminoanthracycline Patients will receive 40mg/m2/day intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate for Amrubicin in Patients With Metastatic or Advanced Sarcoma as First Line Therapy.	Per response evaluation criteria in solid tumors criteria (RECIST 1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	48 months
Progression Free Survival	Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.1) for target lesions and assessed by CT; time elapsed between treatment initiation and tumor progression or death. In target lesions, progression is defined per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In non-target lesions, progression is defined via RECIST v 1.1 as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events		4 months
Overall Survival	This variable reviews the percentage of Overall Survival at 24 months and presents the percentage of participants who survived at 2 years.	two years
Quality of Response With Radiographic Evaluation Using Both Response Evaluation Criteria In Solid Tumors (RECIST) and Choi Criteria.	Per response evaluation criteria in solid tumors criteria (RECIST 1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Exploratory CT evaluations according to Choi response criteria will be also performed and correlated with RECIST response.	48 months
Differential Response to Amurbicin Among Certain Histologic Subtypes of Sarcoma.	Per response evaluation criteria in solid tumors criteria (RECIST 1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	48 months

Collaborators and Investigators

• Sponsor: University of Utah

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: December 10, 2010
• First Submitted That Met QC Criteria: December 13, 2010
• First Posted (ESTIMATE): December 14, 2010

Study Record Updates

• Last Update Posted (ACTUAL): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Antineoplastic Agents; Amrubicin
• Other Study ID Numbers: HCI45197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO