Dendritic Cell Vaccines + Dasatinib for Metastatic Melanoma
Status:
Completed
Trial end date:
2019-07-31
Target enrollment:
Participant gender:
Summary
Current therapeutic approaches available for patients with advanced-stage melanoma remain
inadequate, and existing approaches including those involving immunotherapy with cytokines
and/or targeted strategies have resulted in disappointingly low rates of durable and complete
responses. Correcting immune dysfunction in advanced-stage melanoma patients using
tyrosine-kinase inhibitor (TKI) such as dasatinib is proposed to relicense the patient's
immune system to respond optimally to specific immunization. The integration of antigens
expressed by tumor-associated blood vessel cells provides a means to selectively target the
genetically-/antigenically-heterogeneous population of tumor cells in the advanced-stage
melanoma patient.
This is a single-center, prospective randomized Phase 2 trial evaluating the activity, safety
and immune effects of dasatinib given in combination with an autologous type-1 polarized
Dendritic Cell (αDC1) vaccine. The current trial represents a randomized Phase 2 study to
determine the activity and safety of intradermal (id) administration of αDC1s loaded with a
mixture of six TBVA-derived peptides at the time of, or immediately after, an initial therapy
cycle with the TKI dasatinib.
Dasatinib will be administered at the standard dose and schedule recommended by the FDA (70
mg BID). The autologous type-I DC vaccine will be administered either prior to, or
concomitant with, the initiation of dasatinib administration. All patients will receive
dasatinib at a starting dose of 70 mg twice daily by mouth in the outpatient setting
approximately every 12 hours, at the same time each day.
The DC vaccine will be administered by a single intradermal injection of approximately 10e7
cells, with all the DCs being administered on days 1 and 15 of every cycle on an outpatient
basis in the University of Pittsburgh Clinical and Translational Research Center (UPCI-CTRC).
Patients on Arm A will start dasatinib administration on cycle 2, day 1 (week 5), while those
patients in Arm B will start dasatinib administration on cycle 1, day 1 (week 1).
Men and women at least 18 years of age 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.
Note: The outcome measures and time frames (previously) described in the PRS protocol record
have been revised and articulated in the results section, to more accurately describe and
represent the stated per-protocol investigations and endpoints, quantitatively.