A Phase I Open-Label Safety and Pharmacokinetic Study of Escalating Doses of SGT-53 for Infusion in Subjects With Advanced Solid Tumors
- Have a biopsy confirmed diagnosis thereby providing histological diagnosis of a solid
- Have been offered all standard or approved therapies for which they would be
considered eligible and have specifically declined or decided to postpone.
- Have solid tumors that can be measured on physical examination or by radiographic
- Have a tumor for which docetaxel would be an appropriate therapeutic agent (Phase Ib
- Patients (n=3) entered in phase Ib MTD dose expansion require biopsy accessible
lesion in addition to measurable lesion and must consent to biopsy of tumor and
- Previous docetaxel allowed if > 6 months prior to study entry (Phase Ib only).
- Be 18 years old or older.
- Have an ECOG performance study of 0, 1 or 2 for Phase Ia, 0-1 for Phase Ib.
- Be able to give informed consent.
- Have recovered from any previous therapy side effects or toxicities prior to
initiating protocol study infusions.
- Have a life expectancy of more than 12 weeks.
- Female subjects of childbearing potential must have a negative pregnancy test within
7 days before initiation of study drug dosing. Postmenopausal women must be
amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Male and female subjects of reproductive potential must agree to use measures (e.g.,
condoms or birth control pills) to avoid pregnancy throughout the study and for 3
months following discontinuation of the study drug.
- Organ function characterized by = Grade 1 scores defined by CTCAE v3.0 unless, at
the discretion of the investigator, the condition is not deemed to cause unacceptable
risk to the patient. If deemed not to cause unacceptable risk to the patient, organ
function of grade 2 is acceptable.
- Laboratory values meeting the following criteria:
- Hemoglobin >/= 10.0 gm/dL
- Absolute neutrophil count > 1500/mm3
- White blood cell count > 3000/mm3
- Platelet count >/= 100,000/mm3
- PT/PTT < 1.5 times the upper limit of normal
- LDH = 3 times the upper limit of normal and without clinical or laboratory
evidence of DIC as determined by the clinical investigator
- Total bilirubin = 1.5 times the upper limit of normal (unless elevation is
known to be due to Gilbert's Disease)
- AST and ALT < 2.5 times the upper limit of normal withALP = 2.5 x ULN
- Creatinine = 1.5 mg/dL or creatinine clearance >/= 50 ml/minute
- Have hematological malignancy
- Prior hypersensitivity reaction to docetaxel (Phase Ib only)
- Are pregnant or lactating women
- Have signs and symptoms consistent with an active infection
- Fever (> 38.1 C)
- Treated with antibiotics for infection within one-week prior to study entry
- Known HIV infection
- Have any history of psychiatric disorders that would interfere with informed consent
- Have any other concurrent disease that, in the judgment of the investigator, would
contraindicate the administration of study drug or interfere with the study
- Have fasting glucose levels >/= 180 mg/dL.
- Have diastolic blood pressure of > 90 mm Hg resting at baseline despite medication.
(Acceptable if on hypertensive medication and diastolic blood pressure is = 90 mm
- Have an abnormal stress echo or unfavorable results (at the discretion of the
cardiologist) from the cardiac consultation and evaluation.
- Have known cardiac disease, or a history of cardiac disease.
- Had within six months prior to enrollment any of the following:
- Cerebrovascular accident
- Uncontrolled congestive heart failure (dyspnea on minimal exertion or while
- Unstable angina (chest pain greater than three times weekly while on therapy)
- Have significant baseline neuropathies (>/= grade 2 based upon CTCAE v 3.0).
- Requiring renal dialysis.
- Receiving systemic steroids or other chronic immunosuppressive medications (e.g.,
tacrolimus, cyclosporine) within 30 days prior to study entry
- Receiving hematopoietic growth factors
- Receiving anticoagulants other than to maintain patency of venous access lines
- Received an investigational drug within 30 days prior to study entry
- Received radiation treatment < 4 weeks prior to study entry
- Had prior exposure to gene vector delivery products
- Received treatment with chemotherapeutic agents < 4 weeks prior to study entry except
for mitomycin C or nitrosurea where subjects who received mitomycin C or nitrosoureas
< 6 weeks prior to study entry are not eligible.