A Study of ZYC300 Administered With Cyclophosphamide Pre-Dosing
Information source: MGI PHARMA, Inc.
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer; Ovarian Cancer; Prostate Cancer; Colon Cancer; Renal Cancer; Kidney Cancer
Intervention: Cyclophosphamide (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: MGI PHARMA, Inc.
Summary
ZYC300 is a plasmid DNA formulated within biodegradable microencapsulated particles. The
purpose of this study is to evaluate the feasibility, safety, and tolerability of
administering ZYC300 with a standard chemotherapy drug called Cyclophosphamide (Cytoxan).
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
Clinical Details
Official title: A Phase 1 Open-Label Study of the Safety and Feasibility of ZYC300 Administration With Cyclophosphamide Pre-Dosing
Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety Study
Primary outcome: Determine the feasibility, safety & 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/m2 cyclophosphamide intravenously 3 days prior to study drug.
Secondary outcome: Assess the effect of cyclophosphamide on Treg number & function.Assess the generation of CYP1B1-specific immunity as a result of this vaccination regimen. Assess the effect of this vaccination regimen on tumor response if any in this pt pop.
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/m2
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).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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, 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/mm2
2. WBC ≥ 3,000/mm2
3. Platelet count ≥ 75,000/mm2
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 cretonne ≤ 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 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 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;
4. Have a history of bone marrow or stem cell transplantation
5. Have a history of treatment with fludarabine, 2-chlorodeoxyadenosine,
2-deoxycoformycin or similar compounds:
6. Have a history of treatment with chronic systemic immunosuppressive drugs
7. Have an immunologic disorder such as immunodeficiency, lupus or other chronic
auto-immune disease;
8. Have an active systemic infection requiring treatment;
9. Are known to be positive for HIV antibody;
10. Pregnant or lactating
11. 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;
12. Have had prior ex vivo or in vivo DNA therapy (administration of viral vectors or
plasmid DNA formulations) or cancer vaccines.
13. 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
Locations and Contacts
Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
MGI PHARMA, Inc. Medical Communications, Bloomington, Minnesota, United States
MD Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information
Related publications: 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.
Starting date: September 2006
Ending date: April 2008
Last updated: February 19, 2008
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