Safety, Tolerability, PK, Anti-Tumor Activity of STP705 in Subjects With Advanced/Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy

Inclusion Criteria

• Subjects with histologically or cytologically confirmed advanced/metastatic or surgically unresectable cholangiocarcinoma, hepatocellular carcinoma, or other solid malignancy with one or more qualifying liver metastases who are refractory to standard therapy
• Have at least one liver tumor or metastasis (≤ 5 cm in size) that is not sub-capsular and not near any major blood vessel
• Have no more than 7 liver lesions
• Is deemed safe for percutaneous intra-tumoral injection by local radiologist
• Measurable disease per RECIST v 1.1 (primary or metastatic disease)
• ECOG performance status or 0 - 1
• Life expectancy of at least 3 months
• Age ≥ 18 years
• Signed, written Institutional Review Board (IRB) approved informed consent
• A negative serum pregnancy test (for nonsterile women of child-bearing potential)
• Baseline Q-T corrected interval (QTc) interval of ≤ 480 msec using Frederica's formula
• Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 5 times upper limit of normal because of cancer or metastases to the liver
• Acceptable renal function, defined as: o Serum creatinine ≤ 1.5 ULN or Creatinine Clearance ≥ 30 mL/minute
• Acceptable hematologic status:
• Hemoglobin ≥ 8 g/dL (a transfusion is allowed if Hemoglobin stays stable thereafter)
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
• Platelet count ≥100,000 plt/mm3 x 109/ L (≥ 65,000 if low platelet counts are due to splenic sequestration and portal hypertension)
• Urinalysis with no clinically significant abnormalities
• Acceptable coagulation status with partial thromboplastin time (PTT) and International Normalized Ratio (INR) ≤1.5 times upper limit of normal
• Subject has adequate vitamin D level, as defined by serum total 25-Hydroxyvitamin D [25(OH)D] ≥ 20 to < 60 ng/mL
• Completion of all previous treatments (including surgery, systemic chemotherapy and radiotherapy), as well as supportive care (including transfusion of blood, blood components and granulocyte colony-stimulation factor [G-CSF] treatment) at least 3 weeks before screening (6 weeks for nitrosoureas or mitomycin C), with no signs or symptoms of acute toxicity > Grade 1 (except alopecia)
• For men and women of child-producing potential, the use of effective contraceptive methods during the study
• No aspirin for ≥ 5 days in advance of intra-tumoral administration, as well as discontinuation of antiplatelet and anticoagulant medications for the appropriate amount of time

Exclusion Criteria

• New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months
• Known active, uncontrolled infection with HIV or hepatitis B; patients with hepatitis B allowed if on anti-viral therapy and have a viral load ≤ 500 IU; patients with a history of HIV must be on antiretroviral therapy for at least four weeks and have an HIV viral load ≤ 400 copies/mL, have CD4+ T cell counts ≥ 350 cells/uL and no history of AIDS-defining opportunistic infections within 3 months prior to treatment
• Hepatocellular carcinoma patients with a Child Pugh score > B7
• Had paracentesis in the last 3 months; presence of ascites must be controlled by diuretics
• History of hepatic encephalopathy in the last 6 months
• History of variceal bleeding in the last 6 months
• Concomitant medications that are strong inhibitors or inducers of CYP450 enzymes that cannot be stopped or replaced during the study
• Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study. (Note: Placement of a central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure.)
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Participation in a clinical study involving administration of an investigational compound within the past 30 days prior to study entry.
• Previous intratumoral injection within the past 30 days prior to study entry.
• Unwillingness or inability to comply with procedures required in this protocol
• Known allergy or hypersensitivity to the study drug(s) or one of the ingredients in the formulation
• Existence of any surgical, medical or laboratory condition that, in the judgment of the clinical investigator, might interfere with the safety, distribution, metabolism or excretion of the drug