Vaccine Therapy in Treating Patients With Stage IV Melanoma

Melanoma (Skin) Clinical Trial

Official title:

A Phase I Dose-Ranging Safety Study Using Intranodal Delivery of a Plasmid DNA (Synchrotope TA2M) in Adult Stage IV Melanoma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00023647
• Other study ID #: CDR0000068847
• Secondary ID: CTL-207-216CTL-B
• Status: Completed
• Phase: Phase 1
• First received: September 13, 2001
• Last updated: July 9, 2012
• Start date: July 2000
• Est. completion date: November 2002

Study information

• Verified date: July 2012
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of vaccine therapy given directly into a lymph node in treating patients who have stage IV melanoma.

Description:

OBJECTIVES: I. Determine the safety and tolerability of intranodal Synchrotope TA2M plasmid DNA vaccine in patients with stage IV melanoma. II. Determine the immune response of patients treated with this vaccine. III. Determine the clinical response of patients treated with this vaccine.

OUTLINE: This is dose-escalation, multicenter study. Patients receive Synchrotope TA2M plasmid DNA vaccine intranodally continuously over 96 hours beginning on days 0, 14, 28, and

42. Treatment continues for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 8 patients receive escalating doses of Synchrotope TA2M plasmid DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 8 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 16-24 patients will be accrued for this study within 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 2002
• Est. primary completion date: April 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA - Patient must meet the following during the screening and baseline visits:

1. The patients or their legally acceptable representative must give signed informed consent for participation in the study before any study procedure is performed.

2. Patients must be 18 years of age or older at pre-study

3. Patients must be ambulatory, ECOG performance status of 0 or 1 (Appendix II)

4. Patients have histologically confirmed diagnosis of Stage IV melanoma according to AJCC/UICC modified system with an expected survival time of more than 3 months

5. Patients must be positive for HLA-A2 (Patients tested positive within 5 years of pre-study screening do not need to be tested again for HLA-A2)

6. Patients must agree to use an acceptable method of birth control

1. intrauterine device

2. oral hormonal contraception

3. combination of spermicide and barrier method or

4. abstinence

7. Female patients of childbearing potential must have a confirmed negative urine pregnancy test on Day 0

EXCLUSION CRITERIA - Patients meeting any of the following criteria will NOT be eligible for the study:

1. Patients who have hematological abnormalities as evidenced by:

1. Neutrophils < 1,500/mm3

2. Leukocytes < 3,000/mm3

3. Platelets < 75,000/mm3

4. Hemoglobin < 9.0 g/dL

2. Patients who have hepatic disease as evidenced by:

1. SGOT/SGPT (AST/ALT) > 2.5 x the upper limit of normal (ULN)

2. alkaline phosphatase > 2.5 x ULN

3. Bilirubin > 1.5 x ULN\

4. positive for hepatitis B surface antigen

5. positive for hepatitis C antibody

3. Patients who have known or suspected renal impairment as evidenced by:

1. serum creatinine > 1.5 x ULN, and/or

2. serum urea > 2.6 x ULN

4. Patients with a history of ocular melanoma

5. Patients with brain metastases, unless completed resected

6. Patients with a positive HIV antibody test

7. Patients with medical, sociological, or psychological impediments that may compromise compliance with the protocol

8. Patients who are nursing, pregnant or planning to become pregnant within 6 months of treatment completion

9. Patients who are receiving chemo-, radio- or immunotherapy concurrently or within the preceding four weeks

10. Patients who are taking drugs that affect immune function such as systemic corticosteroids or immunomodulatory drugs concurrently or within the preceding four weeks

11. Patients who are receiving any investigational drug concurrently or within the preceding four weeks

Study Design

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• Synchrotope TA2M
Cancer Vaccine, Immunotherapy
• Synchrotope TA2M
Cancer Vaccine, Immunotherapy
• Synchrotope TA2M
Cancer Vaccine, Immunotherapy

Locations

Country	Name	City	State
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Country where clinical trial is conducted

United States, 

References & Publications (1)

Tagawa ST, Lee P, Snively J, Boswell W, Ounpraseuth S, Lee S, Hickingbottom B, Smith J, Johnson D, Weber JS. Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma. Cancer. 2003 Jul 1;98(1):144-54. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events assessed by complete blood count, blood chemistry, polymerase chain reaction, physical examination and urinalysis		Individual 96-hour infusion periods on days 0, 14, 28 and 42 and on day 56	No
Secondary	Change in magnitude of antigen-specific cytotoxic t-lymphocyte in peripheral blood mononuclear cells		Day 0 (pre-study), last day of individual 96-hour infusion periods (days 4, 17, 31 and 45) and on day 56	No
Secondary	Assessment of delayed-type hypersensitivity to intradermal injections 24 hours after injection		Days 1, 29 and 57	No
Secondary	Change in size of target lesions by x-ray computed tomography before (day 0) and after (day 56)treatment		Change from pre-study (day 0) to day 56	No