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

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) 1.5×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 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.