Amrubicin Chemotherapy as First Line in Metastatic or Unresectable Soft Tissue Sarcoma

Study Overview
=================
Brief Summary
-----------------
Primary Objectives To evaluate the Response Rate (RR) for amrubicin in patients with metastatic or advanced sarcoma as first line therapy. To evaluate Progression Free Survival (PFS). Secondary Objectives To assess the safety and tolerability of amrubicin in this patient population. To evaluate whether certain histologic subtypes of sarcoma demonstrate a differential response to amrubicin. To investigate quality of response with radiographic evaluation using both Response Evaluation Criteria In Solid Tumors (RECIST) and Choi criteria. To evaluate overall survival (OS).

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

Conditions
-----------------
Soft Tissue Sarcoma

Intervention / Treatment
-----------------
* Drug: Amrubicin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>All participants who received Amrubicin. | Drug: Amrubicin<br>* Synthetic 9-aminoanthracycline Patients will receive 40mg/m2/day intravenously<br>|

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 |