Know Cancer

forgot password

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

Phase 1
18 Years
Not Enrolling
Melanoma (Skin)

Thank you

Trial Information

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

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

Inclusion Criteria

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

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

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

Type of Study:


Study Design:

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

Outcome Measure:

Frequency of adverse events assessed by complete blood count, blood chemistry, polymerase chain reaction, physical examination and urinalysis

Outcome Time Frame:

Individual 96-hour infusion periods on days 0, 14, 28 and 42 and on day 56

Safety Issue:


Principal Investigator

Barbara Hickingbottom, JD, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mannkind Corporation


United States: Food and Drug Administration

Study ID:




Start Date:

July 2000

Completion Date:

November 2002

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma



USC/Norris Comprehensive Cancer Center and Hospital Los Angeles, California  90033-0804