Metastatic MelanomaPhase 2NCT01876212
Dendritic Cell Vaccines + Dasatinib for Metastatic Melanoma
A Phase 2 study testing DC vaccine and Dasatinib in people with Metastatic Melanoma, run by Walter J. Storkus at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- DC vaccine and Dasatinib
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2014to 31 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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. Patients that have one biopsiable site that can be amenable to 2 biopsies (pre- and post-) will be considered eligible.
- 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).
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- 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 allowed).
- 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 document.
Who cannot join
- 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 active brain metastases should be excluded. Patients with treated brain metastases with documented stability for 4 weeks are eligible.
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: 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
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.
Read more
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.
- Conditions
- Metastatic Melanoma
- Being tested
- DC vaccine, Dasatinib
- Keywords
- melanoma, metastatic, vaccine, BRAF
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DC vaccineBiological
Also called Type 1-polarized, autologous, DC vaccines incorporating tumor blood vessel antigen (TBVA)-derived peptides
DasatinibDrug
Also called BMS-354825, Sprycel
| Study group | Role | What they receive |
|---|---|---|
| Vaccine + dasatinib | Experimental | Patients will start vaccine on cycle 1, day 1 and dasatinib on cycle 2, day 1 (week 5).
All patients will receive dasatinib at a starting dose of 70 mg twice daily by mouth in the outpatient setting. Dasatinib will be supplied as 50 mg and 20 mg tablets. Patients will take 1 of the 50 mg tablets and 1 of the 20 mg tablets twice daily, 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 each cycle. The intradermal administration will be in the vicinity of the four nodal drainage groups of the four extremities. Receives: Biological: DC vaccine; Drug: Dasatinib |
| Vaccine + dasatinib from cycle 1 | Experimental | Patients will start vaccine on cycle 1, day 1 and dasatinib on cycle 1, day 1.
All patients will receive dasatinib at a starting dose of 70 mg twice daily by mouth in the outpatient setting. Dasatinib will be supplied as 50 mg and 20 mg tablets. Patients will take 1 of the 50 mg tablets and 1 of the 20 mg tablets twice daily, 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 each cycle. The intradermal administration will be in the vicinity of the four nodal drainage groups of the four extremities. Receives: Biological: DC vaccine; Drug: Dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune Response Rate
Immune Response is defined as improved peripheral blood CD8+ T cell responses against 3 or more peptide epitopes after active vaccination with Type I-polarized autologous dendritic cell (αDC1) vaccine incorporating 6 tumor blood vessel-associated antigen (TBVA)-derived peptides.
The measure of Immune Response for this study is expressed as a proportion of responders: The number of HLA-A2+ melanoma patients with improved peripheral blood CD8+ T cell responses (responders) divided by the total number of evaluable patients.
Measured: Up to 13 months
Secondary outcomes (19)
Best Clinical Response
The number of treated patients by best clinical response achieved (tumor measurements via radiologic evaluation) using RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 13 months
Objective Response Rate (ORR)
The proportion of evaluable patients that achieved either partial or complete responses. Calculation: The number of patients who experienced a Partial Response (PR) + the number of patients who experienced a Complete Response (CR) / total number of response-evaluable patients.
Per RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Up to 13 months
Worst Grade of Any Toxicity
Number of participants and severity grades for treatment-relatedness scores of possibly, probably, or definitely.
Measured: Up to 2 years
Progression-free Survival (PFS)
The length of time after study treatment that a patient lives with disease but the disease does not progress. Patients were followed for 1 year after removal from study treatment or until death, whichever occurs first. Per RECIST 1.1, Progressive Disease is defined as a ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 15 months
Overall Survival (OS)
The length of time from the start of study treatment, that patients remain alive.
Measured: Up to 30 months
T Cell-recruiting Chemokine CXCL10/IP-10
Circulating serum concentration (levels) of T cell-recruiting chemokine CXCL10/IP-10 analyzed via ELISA assay. Higher levels of T cell-recruiting chemokine CXCL10/IP-1 correlate with patients exhibiting objective clinical response immunotherapy.
Measured: At baseline (prior to treatment)
T Cell-recruiting Chemokine CXCL10/IP-10
Circulating serum concentration (levels) of T cell-recruiting chemokine CXCL10/IP-10 analyzed via ELISA assay. Higher levels of T cell-recruiting chemokine CXCL10/IP-1 correlate with patients exhibiting objective clinical response immunotherapy.
Measured: At between 5 and 7 weeks, post treatment
Treg CD4FoxP3 Suppressor Cells
Percentage of Treg CD4FoxP3 suppressor cells in patients' peripheral blood. The accumulation of Treg CD4FoxP3 suppressor cell populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At baseline (prior to treatment)
Treg CD4FoxP3 Suppressor Cells
Percentage of Treg CD4FoxP3 suppressor cells in patients' peripheral blood. The accumulation of Treg CD4FoxP3 suppressor cell populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At between 4 and 6 weeks, post treatment
Treg CD4FoxP3 Suppressor Cells
Percentage of Treg CD4FoxP3 suppressor cells in patients' peripheral blood. The accumulation of Treg CD4FoxP3 suppressor cell populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At between 7 and 10 weeks, post treatment
Monocytic Myeloid Derived Suppressor Cells (M-MDSC)
Percentage of Monocytic Myeloid Derived Suppressor Cells (M-MDSC) present in patients' peripheral blood. The accumulation of M-MDSC populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At baseline (prior to treatment)
Monocytic Myeloid Derived Suppressor Cells (M-MDSC)
Percentage of Monocytic Myeloid Derived Suppressor Cells (M-MDSC) present in patients' peripheral blood. The accumulation of M-MDSC populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At between 4 and 6 weeks, post treatment
Monocytic Myeloid Derived Suppressor Cells (M-MDSC)
Percentage of Monocytic Myeloid Derived Suppressor Cells (M-MDSC) present in patients' peripheral blood. The accumulation of M-MDSC populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At between 7 and 10 weeks, post treatment
Polymorphonucler Myeloid-derived Suppressor Cells (PMN-MDSC)
Percentage of Polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) present in patients' peripheral blood. The accumulation/increase of M-MDSC populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At baseline (prior to treatment)
Polymorphonucler Myeloid-derived Suppressor Cells (PMN-MDSC)
Percentage of Polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) present in patients' peripheral blood. The accumulation/increase of M-MDSC populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At between 4 and 6 weeks, post treatment
Polymorphonucler Myeloid-derived Suppressor Cells (PMN-MDSC)
Percentage of Polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) present in patients' peripheral blood. The accumulation/increase of M-MDSC populations correlates with tumor progression (disease progression) and negative prognosis.
Measured: At between 7 and 10 weeks, post treatment
EphA2 Protein Expression in Tumor Biopsies
Level of EphA2 protein expression in tumor tissue biopsies.
Measured: Up to 6 months
Suppressor Cell Populations and Blood Vessels in Melanoma Tumor Biopsies
Percentage of suppressor cell populations and blood vessels in melanoma tumor biopsies.
Measured: Up to 6 months
CD8+ T Cells Infiltration
Percentage of CD8+ T cells infiltrating into melanoma lesions (tumor tissues).
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2013 (estimated)
- Study start16 May 2014
- Primary completion11 Jul 2018
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Walter J. Storkus
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Walter J. Storkus, University of Pittsburgh
- Investigators
- John Kirkwood, MD, Principal investigator, University of Pittsburgh Cancer Institute (UPCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01876212
- Sponsor's protocol ID
- 12-048
- Other IDs
- R01CA169118, UPCI 12-048
- Status last verified
- Aug 2019
- First submitted
- 10 Jun 2013
- Last updated
- 22 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Storkus WJ, Maurer D, Lin Y, Ding F, Bose A, Lowe D, Rose A, DeMark M, Karapetyan L, Taylor JL, Chelvanambi M, Fecek RJ, Filderman JN, Looney TJ, Miller L, Linch E, Lowman GM, Kalinski P, Butterfield LH, Tarhini A, Tawbi H, Kirkwood JM. Dendritic cell vaccines targeting tumor blood vessel antigens in combination with dasatinib induce therapeutic immune responses in patients with checkpoint-refractory advanced melanoma. J Immunother Cancer. 2021 Nov;9(11):e003675. doi: 10.1136/jitc-2021-003675.
PubMed 34782430
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01876212
- Acronym / sponsor ID
- 12-048
- Conditions
- Metastatic Melanoma
- Keywords
- melanoma, metastatic, vaccine, BRAF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Walter J. StorkusUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 May 2014 (actual)
- Primary completion
- 11 Jul 2018 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 12 Jun 2013 (estimated)
- Results
- Posted 6 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaccine + dasatinib | Experimental | Biological: DC vaccine, Drug: DasatinibPatients will start vaccine on cycle 1, day 1 and dasatinib on cycle 2, day 1 (week 5). All patients will receive dasatinib at a starting dose of 70 mg twice daily by mouth in the outpatient setting. Dasatinib will be supplied as 50 mg and 20 mg tablets. Patients will take 1 of the 50 mg tablets and 1 of the 20 mg tablets twice daily, 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 each cycle. The intradermal administration will be in the vicinity of the four nodal drainage groups of the four extremities. |
| Vaccine + dasatinib from cycle 1 | Experimental | Biological: DC vaccine, Drug: DasatinibPatients will start vaccine on cycle 1, day 1 and dasatinib on cycle 1, day 1. All patients will receive dasatinib at a starting dose of 70 mg twice daily by mouth in the outpatient setting. Dasatinib will be supplied as 50 mg and 20 mg tablets. Patients will take 1 of the 50 mg tablets and 1 of the 20 mg tablets twice daily, 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 each cycle. The intradermal administration will be in the vicinity of the four nodal drainage groups of the four extremities. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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. Patients that have one biopsiable site that can be amenable to 2 biopsies (pre- and post-) will be considered eligible.
- 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.
Key exclusion criteria (23 listed)
- 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 active brain metastases should be excluded. Patients with treated brain metastases with documented stability for 4 weeks are eligible.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DC vaccineAlso: Type 1-polarized, autologous, DC vaccines incorporating tumor blood vessel antigen (TBVA)-derived peptides | Biological | Vaccine + dasatinib, Vaccine + dasatinib from cycle 1 |
| DasatinibAlso: BMS-354825, Sprycel | Drug | Vaccine + dasatinib, Vaccine + dasatinib from cycle 1 |
Primary outcome
Immune Response Rate
Time frame: Up to 13 months
Immune Response is defined as improved peripheral blood CD8+ T cell responses against 3 or more peptide epitopes after active vaccination with Type I-polarized autologous dendritic cell (αDC1) vaccine incorporating 6 tumor blood vessel-associated antigen (TBVA)-derived peptides. The measure of Immune Response for this study is expressed as a proportion of responders: The number of HLA-A2+ melanoma patients with improved peripheral blood CD8+ T cell responses (responders) divided by the total number of evaluable patients.
19 secondary outcomes
Best Clinical Response
Time frame: Up to 13 months
Objective Response Rate (ORR)
Time frame: Up to 13 months
Worst Grade of Any Toxicity
Time frame: Up to 2 years
Progression-free Survival (PFS)
Time frame: Up to 15 months
Overall Survival (OS)
Time frame: Up to 30 months
T Cell-recruiting Chemokine CXCL10/IP-10
Time frame: At baseline (prior to treatment)
T Cell-recruiting Chemokine CXCL10/IP-10
Time frame: At between 5 and 7 weeks, post treatment
Treg CD4FoxP3 Suppressor Cells
Time frame: At baseline (prior to treatment)
Treg CD4FoxP3 Suppressor Cells
Time frame: At between 4 and 6 weeks, post treatment
Treg CD4FoxP3 Suppressor Cells
Time frame: At between 7 and 10 weeks, post treatment
Monocytic Myeloid Derived Suppressor Cells (M-MDSC)
Time frame: At baseline (prior to treatment)
Monocytic Myeloid Derived Suppressor Cells (M-MDSC)
Time frame: At between 4 and 6 weeks, post treatment
Monocytic Myeloid Derived Suppressor Cells (M-MDSC)
Time frame: At between 7 and 10 weeks, post treatment
Polymorphonucler Myeloid-derived Suppressor Cells (PMN-MDSC)
Time frame: At baseline (prior to treatment)
Polymorphonucler Myeloid-derived Suppressor Cells (PMN-MDSC)
Time frame: At between 4 and 6 weeks, post treatment
Polymorphonucler Myeloid-derived Suppressor Cells (PMN-MDSC)
Time frame: At between 7 and 10 weeks, post treatment
EphA2 Protein Expression in Tumor Biopsies
Time frame: Up to 6 months
Suppressor Cell Populations and Blood Vessels in Melanoma Tumor Biopsies
Time frame: Up to 6 months
CD8+ T Cells Infiltration
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34782430Storkus WJ, Maurer D, Lin Y, Ding F, Bose A, Lowe D, Rose A, DeMark M, Karapetyan L, Taylor JL, Chelvanambi M, Fecek RJ, Filderman JN, Looney TJ, Miller L, Linch E, Lowman GM, Kalinski P, Butterfield LH, Tarhini A, Tawbi H, Kirkwood JM. Dendritic cell vaccines targeting tumor blood vessel antigens in combination with dasatinib induce therapeutic immune responses in patients with checkpoint-refractory advanced melanoma. J Immunother Cancer. 2021 Nov;9(11):e003675. doi: 10.1136/jitc-2021-003675.
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Metastatic Melanoma, Advanced Locoregional Melanoma
RecruitingPhase 1/2
A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
Recurrent or Metastatic Solid Tumors
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Kirkwood, MD principal investigator
University of Pittsburgh Cancer Institute (UPCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DC vaccine and Dasatinib in people with Metastatic Melanoma, run by Walter J. Storkus at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune Response Rate (time frame: Up to 13 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01876212, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2019.