MC# 14-30 - Phase II Study Of Combined Targeted P53 Gene Therapy (SGT-53) Plus Gemcitabine/Nab-Paclitaxel For Treatment Of Metastatic Pancreatic Cancer
Disease Type(s): Pancreatic
Drug Classification(s): Targeted Therapy, Gene Therapy
Molecular Target(s): TP53
Mechanism of Action
SGT-53 is a cationic liposome encapsulating the wtp53 DNA sequence and delivers the p53 gene to tumor cells via receptor-mediated endocytosis, which then suppresses tumor growth and initiates apoptosis.
In this study, the sponsor and investigators want to learn:
- If the study agent with Gem/Nab-Pacclitaxel shows effect on reducing tumor growth
- How much of the study agent can be given in combination with Gem/Nab-Paclitaxel with an acceptable level of side effects
- The effects of the study agent in combination with Gem/Nab- Paclitaxel
- Patients with histologic or cytologic diagnosis of stage IV metastatic pancreatic adenocarcinoma. Patients with endocrine tumors, sarcoma, lymphoma of the pancreas, or ampullary cancer are ineligible.
- One or more tumors measurable on CT scan per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Life expectancy of at least 3 months.
- Age ³ 18 years.
- Signed, written IRB-approved informed consent.
- A negative pregnancy test (if female and of child-bearing potential).
- Acceptable liver function (obtained within 14 days prior to registration):
- Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 2 baseline)
- AST (SGOT), ALT (SGPT) £ 2.5 x ULN (CTCAE Grade 1 baseline)
- Serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)
- Acceptable hematologic status (obtained within 7 days prior to registration):
- Absolute neutrophil count ³ 1500 cells/mm3
- Platelet count ³ 100,000 (plt/mm3) (CTCAE Grade 1 baseline)
- Hemoglobin ³ 10 g/dL
- Acceptable blood sugar control (based on labs obtained within 7 days prior to registration):
- Fasting glucose value < 160 mg/dL (CTCAE Grade 1 baseline)
- Urinalysis (obtained within 7 days prior to registration): No clinically significant abnormalities.
- PT and PTT ≤ 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT/INR (obtained within 7 days prior to registration).
- For men and women of child-producing potential, willingness to use of effective contraceptive methods during the study.If female (or female partner of male subject), is either not of childbearing potential (defined as postmenopausal for≥1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing 1 of the following medically acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study:
- Oral, implantable or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit.
- Total abstinence from sexual intercourse (≥ 1 complete menstrual cycle before the Baseline/Randomization Visit).
- Intrauterine device (IUD).
- Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream).
- NOT have received any prior cytoxic chemotherapy or investigational therapy. However, this study may be used as 2nd line treatment of patients who progressed on or were intolerant of 1st line FOLFIRINOX. Prior treatment with gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
- They also must NOT have received chemotherapy, radiotherapy, surgery, or investigational therapy for the treatment of metastatic disease.
- Organ function characterized by £ Grade 1 scores defined by CTCAE v4.03 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.
- Patient has received any prior cytoxic chemotherapy for pancreatic cancer with the exception of patients who progressed on or were intolerant of 1st line FOLFIRINOX.Prior treatment with gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients who previously had and were treated with standard therapy for non-pancreatic cancer will be evaluated for entry into the trial on a case-by-case basis.
- New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, unstable angina (chest pain greater than three times weekly while on therapy), evidence of ischemia on ECG, or abnormal stress echocardiogram with evidence of ischemia, or LVEF < 50%.
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
- Treated with antibiotics for infection within one week prior to study entry
- Fever (> 38.1°C)
- Have hematological malignancy
- 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 Hg.)
- 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.
- Treatment with surgery or investigational therapy within 28 days prior to study entry or radiation therapy within 6 months prior to study entry.
- Unwillingness or inability to comply with procedures required in this protocol.
- Known infection with HIV, Hepatitis B, or Hepatitis C.
- Serious nonmalignant disease (e.g., liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
- Patients who are currently receiving any other investigational agent.
- Patients who are currently taking Coumadin or Coumadin derivatives other than to maintain patency of venous access lines.
- Receiving systemic steroids or other chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine) within 30 days prior to study entry
- Receiving hematopoietic growth factors
- Had within six months prior to enrollment any of the following:
- Cerebrovascular accident
- Uncontrolled congestive heart failure (dyspnea on minimal exertion or while supine)
- Have significant baseline neuropathies (> grade 2 based upon CTCAE v 3.0)
- Requires renal dialysis
- Had prior exposure to gene vector delivery products
- Dallas, TX - Mary Crowley Cancer Research - Medical City