A Study of ZYC300 Administered With Cyclophosphamide Pre-Dosing

NCT ID: NCT00381173

Last Updated: 2013-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2008-10-31

Brief Summary

The purpose of this study is to evaluate the feasibility, safety, and tolerability of administering ZYC300 with Cyclophosphamide (Cytoxan).

Detailed Description

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.

Conditions

Breast Cancer; Ovarian Cancer; Prostate Cancer; Colon Cancer; Renal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Cyclophosphamide & ZYC300 (ZYC300 with cyclophosphamide pre-dosing)

Intervention Type: DRUG

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).

Interventions

Cyclophosphamide & ZYC300 (ZYC300 with cyclophosphamide pre-dosing)

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).

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Silverman, MD

Role: STUDY_CHAIR

Eisai Inc.

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

M. D. Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Gribben JG, Ryan DP, Boyajian R, Urban RG, Hedley ML, Beach K, Nealon P, Matulonis U, Campos S, Gilligan TD, Richardson PG, Marshall B, Neuberg D, Nadler LM. Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res. 2005 Jun 15;11(12):4430-6. doi: 10.1158/1078-0432.CCR-04-2111.

Reference Type: BACKGROUND

PMID: 15958627 (View on PubMed)

Other Identifiers

ZYC3-002

Identifier Type: -

Identifier Source: org_study_id