Clinical Trials /

Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer

NCT02340117

Description:

This clinical trial is an open label Phase II study of the combination of intravenously administered SGT-53 and gemcitabine/nab-paclitaxel in patients with metastatic pancreatic cancer as a first-line treatment. The objective of the study is to evaluate the safety, tolerability, toxicity and efficacy (specifically Progression Free Survival at 5.5 month (PFS5.5mos)) of this combination therapy.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer
  • Official Title: Phase II Study of Combined Targeted p53 Gene Therapy (SGT-53) Plus Gemcitabine/Nab-Paclitaxel for Treatment of Metastatic Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: SGT53-02-1
  • NCT ID: NCT02340117

Conditions

  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
nab-paclitaxelAbraxane ABI-007, Albumin-bound paclitaxelSGT-53 with gemcitabine/nab-paclitaxel
GemcitabineGemzarSGT-53 with gemcitabine/nab-paclitaxel

Purpose

This clinical trial is an open label Phase II study of the combination of intravenously administered SGT-53 and gemcitabine/nab-paclitaxel in patients with metastatic pancreatic cancer as a first-line treatment. The objective of the study is to evaluate the safety, tolerability, toxicity and efficacy (specifically Progression Free Survival at 5.5 month (PFS5.5mos)) of this combination therapy.

Detailed Description

      The p53 is a vital human tumor suppressor gene. Loss of p53 suppressor function is present in
      the majority of human cancers. The p53 protein has a diverse range of functions including
      regulation of cell cycle checkpoints, cell death (apoptosis), senescence, DNA repair,
      maintenance of genomic integrity, and control of angiogenesis. Abnormalities of the p53 gene
      may impact the efficacy of standard anticancer treatments such as radiation and chemotherapy.
      P53 mutation and pathway dysfunction are associated with poor clinical outcomes and the
      presence of the p53 mutation correlates with resistance to chemotherapy and radiation. The
      development of somatic gene therapy has created the potential to restore wild type function
      of p53. SGT-53 is a complex of cationic liposome encapsulating a normal human wild type p53
      DNA sequence in a plasmid backbone. This complex has been shown to efficiently and
      specifically deliver the p53 cDNA to the tumor cells. Introduction of the p53 cDNA sequence
      is expected to restore wtp53 function in the apoptotic pathway. P53 restoration has been
      shown most effective in enhancing cytotoxicity in combination with an agent which results in
      DNA damage or initiates apoptosis. This is a Phase II clinical trial of SGT-53 plus the
      recently approved chemotherapeutic combination of gemcitabine/Abraxane® (nab-paclitaxel) as a
      first-line therapy in patients with confirmed metastatic pancreatic cancer. In addition to
      determining Progression Free Survival at 5.5 months (PFS5.5mos), this trial will evaluate the
      response rate, overall survival and time to progression as well as the tolerability and
      safety of SGT-53 in combination with gemcitabine/nab-paclitaxel.
    

Trial Arms

NameTypeDescriptionInterventions
SGT-53 with gemcitabine/nab-paclitaxelExperimentalA course of therapy will include 7 weeks of treatment. In week 1, SGT-53, at 2.4 mg DNA/infusion, will be administered on day 1 and day 5, 1000 mg/m² gemcitabine and 125 mg/m² nab-paclitaxel will be administered on day 3 of each week except week 4. If the combination is well-tolerated, starting at week 2, 3.6 mg DNA/infusion of SGT-53 will be administered bi-weekly on days 1 and 5 in weeks 2-3, weekly on day 3 in week 4, and weekly on day 1 in weeks 5-7. Patients who are responding to treatment may receive one additional course (7 weeks) of SGT-53/gemcitabine/nab-paclitaxel therapy at investigator discretion. If still responding to treatment, they may continue on gemcitabine/nab-paclitaxel alone at investigator discretion.
  • nab-paclitaxel
  • Gemcitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologic or cytologic diagnosis of stage IV metastatic pancreatic
             adenocarcinoma.

          -  One or more tumors measurable on CT scan.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

          -  Life expectancy of at least 3 months.

          -  Age ≥ 18 years.

          -  Signed, written IRB-approved informed consent.

          -  A negative pregnancy test (if female and of child-bearing potential).

          -  Acceptable liver function:

               -  Bilirubin ≤ 1.5 times upper limit of normal

               -  AST (SGOT), ALT (SGPT) ≤ 2.5 x ULN

               -  Serum creatinine ≤ 1.5 X ULN

          -  Acceptable hematologic status:

               -  Absolute neutrophil count ≥ 1500 cells/mm³

               -  Platelet count ≥ 100,000 (plt/mm³)

               -  Hemoglobin ≥ 10 g/dL

          -  Acceptable blood sugar control

             *Fasting glucose value ≤ 160 mg/dL

          -  Urinalysis: No clinically significant abnormalities.

          -  PT and PTT ≤ 1.5 X ULN

          -  For men and women of child-producing potential, willingness to use of effective
             contraceptive methods during the study.

          -  NOT have received any prior cytotoxic 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 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.

        Exclusion Criteria:

          -  Patient has received any prior cytotoxic 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.

          -  Pregnant or nursing women.

          -  Treatment with surgery, or investigational therapy within 28 days prior to study entry
             or radiation therapy within 6 months prior to study entry.

          -  Have received chemotherapy, radiotherapy, surgery or investigational therapy for the
             treatment of metastatic disease.

          -  Unwillingness or inability to comply with procedures required in this protocol.

          -  Known infection with HIV, Hepatitis B, or Hepatitis C.

          -  Serious nonmalignant disease 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 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

          -  Have significant baseline neuropathies

          -  Requires renal dialysis

          -  Had prior exposure to gene vector delivery products
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS) at 5.5 months
Time Frame:5.5 months
Safety Issue:
Description:PFS5.5mos will be assessed by objective radiographic assessment

Secondary Outcome Measures

Measure:Safety
Time Frame:12-24 months
Safety Issue:
Description:Safety will be assessed by analysis of adverse events, clinical laboratory tests, and physical examinations
Measure:Anti-tumor activity
Time Frame:12-24 months
Safety Issue:
Description:Antitumor activity will be assessed by objective radiographic assessment using RECIST 1.1 criteria
Measure:Response Rate
Time Frame:12-24 months
Safety Issue:
Description:Response Rate will be assessed by objective radiographic assessment using RECIST 1.1 criteria
Measure:Progression free survival (PFS)
Time Frame:12-24 months
Safety Issue:
Description:PFS will be assessed by objective radiographic assessment using RECIST 1.1 criteria
Measure:Time to disease progression
Time Frame:12-24 months
Safety Issue:
Description:Time to disease progression will be assessed by objective radiographic assessment using RECIST 1.1 criteria
Measure:Disease control rate
Time Frame:12-24 months
Safety Issue:
Description:Disease control rate will be assessed by objective radiographic assessment using RECIST 1.1 criteria
Measure:Duration of disease control
Time Frame:12-24 months
Safety Issue:
Description:Duration of disease control will be assessed by objective radiographic assessment using RECIST 1.1 criteria

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:SynerGene Therapeutics, Inc.

Last Updated

August 2, 2019