Know Cancer

or
forgot password

A Phase 1 Open-Label Study of the Safety and Feasibility of ZYC300 Administration With Cyclophosphamide Pre-Dosing


Phase 1
18 Years
N/A
Not Enrolling
Both
Breast Cancer, Ovarian Cancer, Prostate Cancer, Colon Cancer, Renal Cancer

Thank you

Trial Information

A Phase 1 Open-Label Study of the Safety and Feasibility of ZYC300 Administration With Cyclophosphamide Pre-Dosing


This is an open-label study of ZYC300 in the treatment of advanced stage malignancy of the
kidney in patients who have not had previous immune-based therapies or treatment of advanced
stage malignancies (cancerous growths) of the ovary, breast, colon, or hormone-refractory
prostate in patients who have failed at least one but no more than two prior regimens of
chemotherapy. Patients who meet all entry criteria will be administered 600 mg/m^2
cyclophosphamide intravenously 3 days before each dose of ZYC300. ZYC300 will be
administered at 400 micrograms DNA/total dose every two weeks for a maximum of six doses (6
cycles).

ZYC300 is a plasmid DNA formulated within biodegradable microencapsulated particles. This
is the first time that ZYC300 and Cyclophosphamide will be given together. Cyclophosphamide
is a chemotherapy drug approved by the FDA that has been used for many years in many
different kinds of cancer. In this trial the study drug will be used to boost the immune
system. Sometimes the immune system cannot fight infected or abnormal cells because of
other cells called T reg cells. The T reg cells limit the immune systems attack on infected
or abnormal cells. In this study, the hope is that Cyclophosphamide will inhibit the T regs
cells so that the ZYC300 can work better to attack the cancer cells.


Inclusion Criteria:



To be included in the study, patients must meet the following criteria:

1. Patients with:

Advanced stage malignancies who have failed treatment, including at least one, but
no more than two, prior regimens of chemotherapy: Ovary, Breast, Colon, Hormone
Refractory Prostate Cancer (HRPC), and renal.

2. Evidence of measurable disease by clinical or radiographic assessment or by tumor
biomarker (ovarian and prostate cancer).

3. Age ≥ 18 years old.

4. A baseline Eastern Cooperative Oncology Group Performance Status of 0 or 1.

5. A life expectancy > 6 months.

6. Adequate hematological function established within 14 days prior to receipt of the
first dose of cyclophosphamide, defined as:

1. Absolute lymphocyte count ≥ 1,000/mm^2

2. WBC ≥ 3,000/mm^2

3. Platelet count ≥ 75,000/mm^2

4. Hemoglobin ≥ 9 g/dL

7. Adequate renal function established within 14 days prior to receipt of the first dose
of cyclophosphamide, defined as serum creatinine ≤ 1.5 X upper limit of normal.

8. Adequate hepatic function established within 14 days prior to receipt of the first
dose of cyclophosphamide, defined as:

1. Total bilirubin ≤ 1.5 X upper limit of normal, and

2. SGOT and SGPT ≤ 2.5X upper limit of normal.

9. An MRI of the brain, if clinically indicated, which is negative for parenchymal
central nervous system metastases within 28 days prior to receipt of the first dose
of cyclophosphamide. If a patient cannot undergo an MRI because of a medical
contraindication, a contrast CT of the brain will be acceptable.

10. A negative pregnancy test (blood or urine) within 14 days prior to first dose of
cyclophosphamide (where applicable).

11. Agree to use appropriate contraception from study entry until the end-of-observation
visit.

12. A signed informed consent form approved by the Institutional Review Board.

Exclusion Criteria:

Patients cannot participate in the study if any of the following apply:

1. Have a history of parenchymal brain metastases.

2. Have received any of the following within 28 days prior to receiving the first dose
of cyclophosphamide:

1. Chemotherapy

2. Radiation therapy

3. Immunotherapy

4. Systemic immunosuppressive drugs

5. Glucocorticoids (inhalers for asthma are permitted)

6. Investigational agent or experimental therapy

3. Have received three or more biologic/targeted therapies, such as monoclonal
antibodies and tyrosine kinase inhibitors.

4. Have initiated or reinitiated the use of hormonal agents within 28 days prior to
receiving the first dose of cyclophosphamide. These drugs are allowed if treatment
was initiated greater than 28 days prior to receipt of the first dose of
cyclophosphamide.

5. Have a history of bone marrow or stem cell transplantation.

6. Have a history of treatment with fludarabine, 2-chlorodeoxyadenosine,
2-deoxycoformycin or similar compounds.

7. Have a history of treatment with chronic systemic immunosuppressive drugs.

8. Have an immunologic disorder such as immunodeficiency or other chronic auto-immune
disease if deemed to be clinically significant.

9. Have an active systemic infection requiring treatment.

10. Are known to be positive for HIV antibody.

11. Pregnant or lactating.

12. Have a history of alcohol abuse, illicit drug use, or psychiatric disorder that would
in the Investigator's opinion jeopardize protocol compliance or compromise the
patient's ability to give informed consent.

13. Have had prior ex vivo or in vivo DNA therapy (administration of viral vectors or
plasmid DNA formulations) or cancer vaccines.

14. Previous exposure to ZYC300 or amolimogene (HPV E6E7 plasmid; formerly known as
ZYC101a).

Please note: There may be additional inclusion/exclusion criteria. The study center will
determine if patients meet all of the criteria. If patients do not qualify for the trial,
study personnel will explain the reasons. If patients do qualify, study personnel will
explain the trial in detail using an IRB-approved informed consent, and answer any
questions. Patients can then decide if they wish to participate.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the feasibility, safety and tolerability of administering ZYC300 intramuscularly every other wk for 6 doses (400 micrograms DNA/total dose) to the study pop. pre-dosed with 600 mg/m^2 cyclophosphamide intravenously 3 days prior to study drug.

Outcome Time Frame:

Within 14 days and 12 weeks post last dose of study drug (and 16 weeks post last dose for response confirmation, if applicable).

Safety Issue:

Yes

Principal Investigator

Michael Silverman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Eisai Inc.

Authority:

United States: Food and Drug Administration

Study ID:

ZYC3-002

NCT ID:

NCT00381173

Start Date:

November 2006

Completion Date:

October 2008

Related Keywords:

  • Breast Cancer
  • Ovarian Cancer
  • Prostate Cancer
  • Colon Cancer
  • Renal Cancer
  • MGI PHARMA
  • ZYC3-002
  • ZYC300
  • plasmid DNA
  • cyclophosphamide
  • Cytoxan
  • advanced breast cancer
  • advanced ovarian cancer
  • hormone refractory prostate cancer
  • advanced colon cancer
  • advanced renal cancer
  • advanced stage malignancies
  • immune therapy
  • gene therapy
  • biologic therapy
  • T-regulatory cells
  • cancer vaccine
  • vaccine
  • Advanced stage malignancies-ovary, breast, colon, prostate
  • Breast Neoplasms
  • Colonic Neoplasms
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Ovarian Neoplasms
  • Prostatic Neoplasms

Name

Location

Dana-Farber Cancer InstituteBoston, Massachusetts  02115
M. D. Anderson Cancer CenterHouston, Texas  77030