Efficacy and Safety Study of GPX-150 to Treat Soft Tissue Sarcoma

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety and efficacy of GPX-150 administered intravenously every 3 weeks in the treatment of patients with soft tissue sarcoma.

Detailed Description
-----------------
This is an open-label, single arm study of GPX-150 in patients with soft tissue sarcoma. Approximately 22 patients will be treated in this study. The population for this study is adult patients with histologically proven advanced and/or metastatic malignant soft tissue sarcoma of intermediate or high histologic grade. All patients who meet all entry criteria will receive GPX-150 at a starting dose of 265 mg/m2 every 21 days for 16 cycles or until death, disease progression, or unacceptable toxicity or subject withdrawal. Prior to initiation of treatment, subjects will undergo screening and baseline evaluations. During all study visits, subjects will be evaluated for safety. The dose of GPX-150 may be reduced when subjects meet specified dose reduction safety criteria. Subjects will be evaluated regularly for safety and tolerability. Tumor measurements will be calculated at baseline (within 28 days prior to treatment initiation), then at regular intervals while receiving treatment for up to 1 year. After discontinuing the treatment phase of the study, safety assessments and tumor measurements will be performed 3 weeks after the last dose of study drug.

Official Title
-----------------
Phase 2 Efficacy and Safety Study of Intravenous GPX-150, an Anthracycline Analog, in Patients With Soft Tissue Sarcoma

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

Intervention / Treatment
-----------------
* Drug: GPX-150 for Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years. Histological documentation of soft tissue sarcoma (biopsy may be historical and may have been obtained from primary tumor or a metastatic site). Advanced and/or metastatic malignant soft tissue sarcoma of intermediate or high histologic grade. Excluded are the following sarcoma subtypes: Well-differentiated liposarcoma or atypical lipomatous tumor Embryonal or alveolar rhabdomyosarcoma Ewing sarcoma of soft tissue or bone Gastrointestinal stromal tumor (GIST) Dermatofibrosarcoma protuberans Alveolar soft part sarcoma Solitary fibrous tumor Clear cell sarcoma Kaposi sarcoma Extraskeletal myxoid chondrosarcoma PEComa (perivascular epithelial cell tumor) Myoepithelioma / mixed tumor Measurable disease as per RECIST 1.1. Subject has received either: No prior chemotherapy for current sarcoma, or A single course of gemcitabine and/or docetaxel as adjuvant therapy that was completed at least 6 months prior to planned first dose ECOG Performance Status of 0 - 2. Adequate cardiac function: LVEF above the institution's lower limit of normal QTcF ≤ 450 msec for males or 470 msec for females. Willing and able to provide written informed consent. Male and female subjects must agree to use a highly reliable method of birth control for the duration of the study. Women of childbearing potential must have a serum pregnancy test performed within 28 days prior to the first day of study drug dosing. Exclusion Criteria: Sarcomas arising from bone or cartilage, e.g. chondrosarcoma, osteosarcoma, chordoma. Subject is eligible for a potentially curative therapy. Prior primary chemotherapy. Prior radiotherapy to > 25% of bone marrow volume. Treatment within 28 days prior to Dose 1 with: Palliative surgery or radiotherapy. Approved anticancer therapy including chemotherapy or immunotherapy. Contraindicated treatments noted in the product labelling for doxorubicin, including trastuzumab and inhibitors and inducers of CYP3A4, CYP2D6, or P-gp. An investigational therapy. Any major surgery (e.g. requiring general anesthesia). Inadequate bone marrow, liver, and renal function, as assessed by the following laboratory parameters: Absolute neutrophil count (ANC) < 1,500/mm3. Platelet count < 100,000/mm3. Total bilirubin > 1.5×ULN (upper limit of normal). ALT and AST > 2.5×ULN. For patients with documented liver metastases, ALT and AST > 5×ULN. Serum creatinine > 1.5 x ULN. International Normalized Ratio (INR) and activated partial thromboplastin time [PTT] ≥ 1.5×ULN, if not therapeutically anticoagulated. Serum albumin < 3.0 gm/dL. Congestive heart failure > Class II New York Heart Association Functional Classification, current pericarditis, myocardial infarction within 6 months, or symptomatic coronary artery disease. Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol. Active infection requiring systemic antibacterial/antibiotic, antifungal, or antiviral therapy. Documented metastases to brain or meninges. Any malignancy other than soft tissue sarcoma within the last 5 years prior to screening, with the exception of cervical carcinoma in situ, basal cell carcinoma, or superficial bladder tumors that have been successfully and curatively treated with no evidence of recurrent or residual disease. Body surface area (BSA) ≥ 2.4 m2. Currently pregnant or nursing. Known allergy to any of the study drugs or their excipients.

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: GPX-150<br>GPX-150 for Injection, 265 mg/m2, every 21 days for 16 cycles or until death, disease progression, or unacceptable toxicity, or subject withdrawal. | Drug: GPX-150 for Injection<br>* GPX-150 at a starting dose of 265 mg/m2 every 21 days for 16 cycles or until death, disease progression, or unacceptable toxicity. The dose of GPX-150 may be reduced by 25% if any dose reduction criteria are met. Two reductions are allowed per subject during the course of the study.<br>* Other names: 5-imino-13-deoxy-doxorubicin HCl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Progression-free at 12 Months Per RECIST 1.1 | The primary efficacy endpoint is the number of patients who were progression-free at 12 months, which is obtained by inversion of the Kaplan-Meier curve for progression-free survival (PFS) at 12 months. Of note, the statistical comparison to historical sarcoma data described in the protocol was not performed due to an enrollment of less than the planned sample size of 30 subjects. Progression is defined using RECIST 1.1, as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | 12 months from the beginning of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Progression-free at Six Months Per RECIST 1.1 | This secondary efficacy endpoint is the progression-free rate (PFR) at 6 months, obtained from the Kaplan-Meier curve for progression-free survival (PFS). | 6 months from the beginning of the study treatment | 
| Number of Subjects Experiencing Adverse Events | Subjects who received at least one dose were included in safety analyses. Adverse events were tabulated by System Organ Class (SOC) and Preferred Term (PT) and coded using MedDRA Version 19.1. Safety and tolerability was determined by frequency, nature, and severity of adverse events and the profile of toxicities. | From the beginning of study treatment and up to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
soft tissue sarcoma