Soft Tissue Sarcoma
Conditions
Brief summary
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).
Interventions
DRUGAmrubicin
Synthetic 9-aminoanthracycline Patients will receive 40mg/m2/day intravenously
Sponsors
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate for Amrubicin in Patients With Metastatic or Advanced Sarcoma as First Line Therapy. | 48 months | 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 |
| Progression Free Survival | six months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | 4 months | — |
| Overall Survival | two years | This variable reviews the percentage of Overall Survival at 24 months and presents the percentage of participants who survived at 2 years. |
| Quality of Response With Radiographic Evaluation Using Both Response Evaluation Criteria In Solid Tumors (RECIST) and Choi Criteria. | 48 months | 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. |
| Differential Response to Amurbicin Among Certain Histologic Subtypes of Sarcoma. | 48 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Groups All patients that received treatment. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | All Groups |
|---|---|
| Age, Continuous | 52 years |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 7 / 24 |
Outcome results
Primary
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.
Time frame: six months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Progression Free Survival | 42.7 percentage of pt with 6 mnth PFS |
Primary
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
Time frame: 48 months
Population: One patient discontinued study treatment after the first cycle due to side effects and was not evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Response Rate for Amrubicin in Patients With Metastatic or Advanced Sarcoma as First Line Therapy. | 13 percentage of pt with a partial response |
Secondary
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.
Time frame: 48 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Differential Response to Amurbicin Among Certain Histologic Subtypes of Sarcoma. | liposarcoma | 1 participants |
| All Patients | Differential Response to Amurbicin Among Certain Histologic Subtypes of Sarcoma. | myxoid liposarcoma with TLS-CHOP translocation | 1 participants |
| All Patients | Differential Response to Amurbicin Among Certain Histologic Subtypes of Sarcoma. | leiomyoscarcoma | 1 participants |
Secondary
Number of Participants With Serious Adverse Events
Time frame: 4 months
Population: One patient discontinued study treatment after the first cycle due to side effects and was not evaluable for response, but was evaluable for safety and toxicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Number of Participants With Serious Adverse Events | 7 participants who experienced an SAE |
Secondary
Overall Survival
This variable reviews the percentage of Overall Survival at 24 months and presents the percentage of participants who survived at 2 years.
Time frame: two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Overall Survival | 52.8 percentage of participants |
Secondary
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.
Time frame: 48 months
Population: This exploratory objective was not assessed.