Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma (NCT03620019) | Clinical Trial Compass
CompletedPhase 2
Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma
United States25 participantsStarted 2018-09-10
Plain-language summary
This is a multicenter open-label, single-arm, phase II study designed to investigate the pharmacodynamic and antitumor effects of denosumab alone and in combination with an anti-Programmed death-1 or Programmed death ligand 1 (PD1) agent (pembrolizumab or nivolumab) in patients with unresectable Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve regional and distant metastatic melanoma (The American Joint Committee on Cancer (AJCC) stage III/IV). The pharmacodynamic and antitumor effects will be investigated by performing translational research on peripheral blood and tumor tissue collected before and during denosumab alone and in combination with anti-PD-1 treatment.
Who can participate
Age range18 Years – 99 Years
SexALL
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Inclusion criteria
✓. Signed written informed consent and HIPAA authorization for release of personal health information.
✓. Age ≥ 18 years at the time of consent.
✓. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
✓. Histologically confirmed melanoma of cutaneous or mucosal primary; (e.g. sinus, vagina, anus, gastrointestinal tract); metastatic melanomas from unknown primary are allowed because melanoma of unknown primary is biologically similar to cutaneous melanomas.
✓. AJCC stage III/IV unresectable (or resectable) disease. Both should be measurable by RECIST v1.1 criteria. Patients with resectable bulky stage IIIB, state IIIC or stage IIID melanoma (≥2-cm in shortest diameter for lymph nodes infiltrated by tumor and ≥2-cm in longest diameter for non-lymph nodes infiltrated by tumor) can also be entered into the study at the discretion of the Principal Investigator.
✓. Must have available and consent to collect archived tumor blocks from previous surgeries confirming or treating metastatic disease (e.g. radical lymph node dissection); if not available they can be enrolled into the trial, if they consent to have a tumor biopsy before treatment initiation.
✓. Must agree to undergo one on-treatment biopsy on week 4of the study; the biopsy at week 16 is optional.
What they're measuring
1
The Antitumor Effect of Denosumab Alone as Represented by the Change in Recent Thymic Emigrant Cells in Peripheral Blood
Timeframe: 3 weeks after start of denosumab
2
The Antitumor Effect of Denosumab Alone as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
Timeframe: 3 weeks after start of denosumab
3
The Antitumor Effect of Denosumab Combined With Anti-PD-1 Inhibitor as Represented by the Change in Recent Thymic Emigrant Cells in Peripheral Blood - CD8+
Timeframe: 16, 28 and 40 weeks after start of denosumab
4
The Antitumor Effect of Denosumab Combined With Anti-PD-1 Inhibitor as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
Timeframe: Baseline, 16 weeks after start of denosumab combined with anti-PD-1 inhibitor
. Must agree to have 100 mL blood drawn for study purposes on week 1 , day 20+or-2 (week 4), week 16, week 28, week 40 and end of treatment.
Exclusion criteria
✕. History of prior malignancy, with the exception of the following:
✕. Has known active central nervous system (CNS) metastases that are symptomatic and require antiepileptic drugs or corticosteroids (any dose). Subjects with previously treated brain metastases may participate provided they are asymptomatic (i.e., no neurologic symptoms) for at least 2 weeks prior to the first dose of trial treatment and are not using steroids for at least 7 days prior to trial treatment. Patients with previously treated brain metastases should have evidence of stable brain metastases (without evidence of progression by imaging) for at least 2 weeks prior to the first dose of trial treatment. Patients with previously treated but grown brain metastases (or new brain metastases if there is no prior history of brain metastases) are still allowed in the study as long as the net growth of pre-existing brain lesions (or new brain lesions if there is no prior history of brain metastases) does not exceed 1-cm in largest diameter as measured by brain MRI with IV contrast (for example, a patient with pre-existing brain lesion(s) that has grown by 6-mm in the largest diameter and also has a new lesion that measures 4-mm in largest diameter can still be enrolled in the study; alternatively, a patient that has a new brain lesion that measures 1-cm in the largest diameter and no growth of pre-existing brain lesions can still be enrolled in the study). This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. Subjects with leptomeningeal disease, detected either by brain MRI or by cytology (e.g. lumbar puncture) are also excluded.
✕. Treatment with any investigational drug, immunotherapy or chemotherapy within 28 days prior to study treatment (i.e., initiation of denosumab). Treatment with any targeted therapy (e.g. Mitogen-Activated Protein Kinases (MAPK) inhibitors) is allowed as long as at least 15 days have elapsed since last dose of drug.
✕. Patients discontinuing prior therapy with tyrosine kinase inhibitors for melanoma should be off these medications for at least 15 days before starting study treatment.
✕. Prior PD-1/PD-L1 therapies in the adjuvant setting; targeted therapies or prior ipilimumab in the adjuvant setting are allowed.
✕. Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk, if he/she were to participate in the study. This includes, but is not limited, to serious medical conditions or psychiatric illness likely to interfere with participation in this clinical study.
✕. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy equivalent to daily doses of prednisone of 10 mg or greater (or an equivalent dose of other corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
✕. Has a known history of active tuberculosis (Mycobacterium Bacillus Tuberculosis).