Know Cancer

forgot password

A Phase I Open-Label Safety and Pharmacokinetic Study of Escalating Doses of SGT-53 for Infusion in Subjects With Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)

Thank you

Trial Information

A Phase I Open-Label Safety and Pharmacokinetic Study of Escalating Doses of SGT-53 for Infusion in Subjects With Advanced Solid Tumors

The p53 gene is a vital tumor suppressor gene in humans. Numerous human tumors possess a
loss or mutation of wild type p53 (wtp53). In addition to playing a crucial role in cell
cycle control, the p53 gene is a critical component in two of the pathways involved in
regulating tumor cell growth: cell death (apoptosis) and the regulation of angiogenesis.
The loss of such critical tumor suppressor activity is believed to be responsible for p53's
involvement in such a broad array of human tumors and resistance to chemo/radiotherapy.
SGT-53 is a complex composed of a wild type p53 gene (plasmid DNA) encapsulated in a
liposome that is targeted to tumor cells by means of an anti-transferrin receptor
single-chain antibody fragment (TfRscFv) attached to the outside of the liposome.
Pre-clinical studies have indicated that SGT-53 could sensitize tumors to the effects of

The Phase 1a portion of this clinical study was designed to evaluate the safety and maximum
tolerated dose (MTD) of SGT-53. In addition, pharmacokinetics of escalating doses of SGT-53
will be measured and correlated with tumor response and toxicity.

The Phase Ib portion of this clinical study is designed to evaluate the safety of SGT-53 in
combination with docetaxel, determine the recommended Phase II doses of these two agents,
and evaluate the effect of the combination of SGT-53 and docetaxel on tumor size or

Inclusion Criteria:

- Have a biopsy confirmed diagnosis thereby providing histological diagnosis of a solid
tumor malignancy.

- 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
imaging studies.

- 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
normal skin.

- 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 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 evidence of DIC as determined by the clinical investigator

- Total bilirubin known to be due to Gilbert's Disease)

- AST and ALT < 2.5 times the upper limit of normal withALP
- Creatinine /= 50 ml/minute

Exclusion Criteria:

- 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
or follow-up.

- 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 Hg.)

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety will be assessed by analysis of adverse experiences, clinical laboratory tests, and physical examinations.

Outcome Time Frame:

7 weeks

Safety Issue:


Principal Investigator

John J. Nemunaitis, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mary Crowley Medical Research Center


United States: Food and Drug Administration

Study ID:




Start Date:

February 2008

Completion Date:

December 2013

Related Keywords:

  • Neoplasm
  • Neoplasm
  • Neoplasms



Mary Crowley Medical Research Center Dallas, Texas  75246