Phase I Evaluation of Safety of Intravenous Infusion of a Pathotropic Vector Bearing a Cytocidal Cyclin G1 Construct (Rexin-G) as Intervention for Locally Advanced and Metastatic Pancreatic Cancer Refractory to Standard Chemotherapy
18 Years
N/A
Both
Pancreatic Cancer
Trial Information
Phase I Evaluation of Safety of Intravenous Infusion of a Pathotropic Vector Bearing a Cytocidal Cyclin G1 Construct (Rexin-G) as Intervention for Locally Advanced and Metastatic Pancreatic Cancer Refractory to Standard Chemotherapy
Pancreatic cancer is the fourth leading cause of cancer death in the United States. Every
year, about 30,000 new patients are diagnosed with pancreatic cancer, and most will die
within the year. The few patients that live beyond one year are those who have operable
tumors whose cancer has not spread beyond the pancreas. There is no effective treatment for
pancreatic cancer that impacts survival beyond a few more months. Therefore, innovative
treatments are urgently needed. A number of experimental therapies are currently under
investigation, and gene therapy is a viable therapeutic option.
A gene called cyclin G1 has been shown to play a very important part in cancer growth. In
animal experiments, when this cyclin G1 gene is blocked, the cancer cells grow much slower
or even die. This study will test the drug, Rexin-G, which contains a gene that works by
getting rid of the cyclin G1 gene. The new gene will get into the tumor cells using a
"vehicle" to carry it into the cells. The "vehicle" that will be used is a virus that has
been changed so that it is not likely to cause disease. This "vehicle" is called a vector.
When injected into a vein, the Rexin-G vector is designed to seek out and accumulate in
cancerous tumors, therefore, increasing the concentration of the drug in the area of the
cancer and not in normal neighbouring organs. When the killer gene gets into the cancer
cell, it becomes part of the cell's genes and tells the cancer cell to begin using the new
gene instead of the cyclin G1 gene. It is hoped that the Rexin-G will arrest the growth of
the cancer or eradicate the tumor.
The goals of the study are to determine how much Rexin-G can be given to a patient, to
assess how long Rexin-G stays in the body when injected into a vein, and if the drug would
cause antibodies to form, transfer the gene to normal tissues or pass on the gene to another
person or the person's offspring. The final goal is to determine if the Rexin-G vector can
shrink the tumor by comparing the size of the tumor nodules measured by CT scan or MRI
before and after the Rexin-G treatment.
Inclusion Criteria:
- Age 18 years or older.
- Locally advanced or metastatic pancreatic cancer.
- Histologic or cytologic confirmation at diagnosis or recurrence of pancreatic cancer
- Measurable disease (RECIST) criteria. Tumor lesions that are situated in a
previously irradiated area are not considered measurable, except if there is
radiologically confirmed progression of disease within the radiation fields after
radiation was completed.
- Failed gemcitabine chemotherapy as indicated by disease progression ≤ 6 months from
last gemcitabine treatment
- Two or less than 2 chemotherapy regimens for recurrent/progressive disease.
- Adequate hepatic function based on laboratory values obtained less than 7 days prior
to registration:
- Total bilirubin <2.0 mg/dL;
- AST < 2 x ULN;
- AST < 2 x ULN;
- Hgb > 9.0 gm/dL;
- PT < ULN;
- PTT
- Albumin > 3.0 gm/dL;
- Alkaline phosphatase < 3 x ULN;
- Absolute granulocyte count > 1000/uL;
- Platelet count > 100,000/uL;
- Serum creatinine < 1.2 mg/dL for females; < 1.4 mg/dL for males.
- ECOG performance status (PS) 0 or 1.
- Ability to provide informed consent.
- Life expectancy 12 weeks or greater.
- Male participants should be willing to provide semen samples at required intervals.
Inability of the patient to provide all semen samples does not make the patient
ineligible. (EXCEPTION: If the patient has been vasectomized. To be noted in the
study file).
- Fertile patients agree to use barrier contraception (condoms plus spermicidal jelly)
during the vector infusion period and for six weeks after infusion.
- Accessibility of peripheral or central IV line which is adequate for infusions of
investigational agent.
Exclusion Criteria:
- Prior malignancy. (EXCEPTION: Patients who are disease free ≥ 5 years and/or
patients with non-melanoma skin cancer, Stage I breast cancer, CIS of cervix)
- Any of the following:
- Pregnant women;
- Nursing women;
- Men or women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragm, birth control pills, injections, intrauterine
device [IUD], or abstinence, etc.). This study involves an investigational
agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus
and newborn are unknown.
- Patients who are HIV+, HBV+ or HCV+.
- Clinically significant ascites causing symptoms or requiring therapeutic
paracentesis.
- Medical, psychiatric, or social conditions that would compromise successful adherence
to this protocol.
- Concomitant use of other chemotherapeutic, viral or immunotherapeutic agents is not
allowed during the 6-week study period.
- ≤ 4 weeks from radiation therapy of their pancreatic primary or ≤ 2 weeks from
palliative radiation therapy to metastatic sites.
- ≤ 4 weeks from prior chemotherapy.
- History of congestive heart failure.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the dose limiting toxicity and maximum tolerated dose of Rexin-G administered as intravenous infusions; To evaluate pharmacokinetics of Rexin-G
Outcome Time Frame:
22 months
Safety Issue:
Yes
Principal Investigator
Evanthia Galanis, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic Rochester Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
MC044C
NCT ID:
NCT00121745
Start Date:
July 2005
Completion Date:
July 2007
Related Keywords:
- Pancreatic Cancer
- gene transfer
- cell cycle control
- cancer gene therapy
- pathotropic targeting
- tumor targeted retroviral vector
- Pancreatic Neoplasms
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
