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A Randomized Phase 2 Pilot Study of Type I-Polarized Autologous Dendritic Cell Vaccines Incorporating Tumor Blood Vessel Antigen (TBVA)-Derived Peptides in Combination With Dasatinib in Patients With Metastatic Melanoma

Phase 2
18 Years
Not Enrolling
Metastatic Melanoma

Thank you

Trial Information

A Randomized Phase 2 Pilot Study of Type I-Polarized Autologous Dendritic Cell Vaccines Incorporating Tumor Blood Vessel Antigen (TBVA)-Derived Peptides in Combination With Dasatinib in Patients With Metastatic Melanoma

Inclusion Criteria:

- Patients must be HLA-A2+ and have histologically confirmed melanoma that is
metastatic (Stage IV) or unresectable Stage IIIB/C and for which standard curative or
palliative measures do not exist or are no longer effective.

- Patients must have measurable disease by RECIST 1.1, defined as at least one lesion
that can be accurately measured in at least one dimension (longest diameter to be
recorded for non-nodal lesions and short axis for nodal lesions) as > 20 mm with
conventional techniques or as > 10 mm with spiral CT scan, MRI, or calipers by
clinical exam. See Section 11 for the evaluation of measurable disease.

- Patients should have at least 2 subcutaneous, intracutaneous, and accessible tumor
deposits, lymph node or other site available for biopsy purposes.

- Prior chemotherapy, immunotherapy, or targeted therapy is allowed as long as it did
not include dasatinib.

- Age > 18 years. Because no dosing or adverse event data are currently available on
the use of dasatinib in patients < 18 years of age, children are excluded from this
study, but will be eligible for future pediatric trials.

- ECOG performance status < 2 (Karnofsky > 60%, see Appendix A).

- Life expectancy of greater than 12 weeks.

- Patients must have normal organ and marrow function as defined below:

- Leukocytes ≥ 3,000/µL

- absolute neutrophil count ≥ 1,500/µL

- absolute lymphocyte count ≥ 500/µL

- platelets ≥ 100,000/µL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal

- Creatinine ≤ 2.0 X institutional upper limit of normal

- Serum magnesium, potassium and adjusted (or ionized) calcium ≥ the institutional
lower limit of normal. (Supplementation of electrolytes prior to screening is

- Sexually active women and men of childbearing potential must agree to use an
effective method of birth control during the course of the study and for up to 3
months following the last dose of the study drug, in a manner such that risk of
pregnancy is minimized. Surgical sterilization, intrauterine device or barrier method
(e.g. condom and/or diaphragm with spermicidal agents) are acceptable forms of birth
control. Women of childbearing potential must have a negative pregnancy test (serum)
within 7 days prior to treatment. A pregnancy test is not required for registration.
Women who have not menstruated for more than 2 years will be considered
postmenopausal, thus not of childbearing potential.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients with documented c-KIT mutations.

- Patients who are receiving any other investigational agents.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dasatinib or any of the components of the vaccine being administered
as part of this study.

- Women who are pregnant or nursing/breastfeeding.

- History of significant bleeding disorder unrelated to cancer, including:

- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
VIII antibodies)

- Patients currently taking medications that inhibit platelet function (i.e., aspirin,
dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab,
ticlopidine, and any non-steroidal anti-inflammatory drug) because of a potential
increased risk of bleeding from dasatinib.

- Patients currently taking anticoagulants (warfarin, heparin/low molecular weight
heparin [e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]) because of a
potential increased risk of bleeding from dasatinib.

- Diagnosis of unstable angina or myocardial infarction within 6 months of study entry.

- Patients currently taking one or more of the following drugs that are generally
accepted to have a risk of causing Torsades de Pointes:

- quinidine, procainamide, disopyramide

- amiodarone, sotalol, ibutilide, dofetilide

- erythromycins, clarithromycin

- chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

- cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

- Diagnosed or suspected congenital long QT syndrome.

- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) within 30 days
prior to study registration.

- Any history of clinically significant ventricular arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or Torsades de pointes)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with dasatinib. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Increase of CD8+ T cell response from addition of dasatinib

Outcome Description:

Translation and clinical vaccine trials have demonstrated that DC/peptide-based vaccines effectively activate specific CD8+ T cells in tumor-bearing hosts that may be detected in peripheral blood, and that individuals that exhibit objective clinical response to such vaccine therapies tend to derive from the cohort of patients that display detectable increases in T cell responses post-vaccination. Our own pre-clinical studies support the effectiveness of DC1/peptide vaccination to elicit protective/therapeutic T cell-mediated immunity in melanoma models in vivo, supporting the hypothesis that DC1/peptide vaccination of advanced stage melanoma patients will result in increased quantities of specific CD8+ T cells in patient peripheral blood and that those individuals in which improved response to many peptides can be observed are those that are more likely to demonstrate clinical benefit.

Outcome Time Frame:

Change from Baseline at weeks 2 & 4 for at least 6 cycles.

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

July 2013

Completion Date:

July 2016

Related Keywords:

  • Metastatic Melanoma
  • Melanoma



Hillman Cancer Center Pittsburg, Pennsylvania  15232