Metastatic malignant melanoma MedDRA version: 21.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10025650 Term: Malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10027480 Term: Metastatic malignant mel
Conditions
Interventions
Trade Name: XGEVA
Product Name: DENOSUMAB
Pharmaceutical Form: Solution for injection
Product Name: OPDIVO
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NIVOLUMAB
CA
Sponsors
Alcedis GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Provision of tumor tissue from metastatic site of disease for biomarker analyses and confirmation by central laboratory. Tumor tissue must be obtained before PD-1 inhibitor therapy (either baseline FFPE sample or archival tissue (ideally obtained after preceding medical tumor therapies). • Inoperable metastatic stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown primary site or melanoma of mucosal or uveal origin. • Planned therapy with PD-1 blocking antibody (nivolumab or nivolumab + ipilimumab or pembrolizumab) and denosumab as standard of care. • Measurable disease according to RECIST1.1 and at least one documented bone metastasis. • Age 18 years or above. • Written, informed consent. • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study • Minimum life expectancy of 6 months • ECOG performance status of 0-2 • Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration: WBC = 2000/µL Neutrophils = 1000/µL Platelets = 100 x103/µL Hemoglobin = 9.0 g/dL Serum creatinine = 2.0 x ULN OR Creatinine clearance (CrCl) = 35mL/min (using the Cockcroft-Gault formula) • AST/ALT = 3 x ULN, in case of liver metastases = 5 x ULN Total Bilirubin = 2.0 x ULN (except subjects with Gilbert Syndrome, who may have total bilirubin up to 5 x ULN) • Serum calcium or albumin-adjusted serum calcium within normal limits • Prior radiotherapy must have been completed prior to study drug administration • Negative pregnancy test for female subjects within the week before treatment start and effective contraception for both male and female subjects if the risk of conception exists Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Prior therapy with CTLA4-inhibitor or PD-1-inhibitor or denosumab for distant metastatic disease. Treatments in the adjuvant setting are allowed in case treatment was discontinued at least 4 weeks before inclusion in this study. • No other concurrent medical treatments for metastatic disease such as targeted therapies or chemotherapies are allowed. Treatments in the adjuvant setting are allowed in case treatment was discontinued at least 4 weeks before inclusion in this study. • Active CNS metastases requiring local therapy or steroid therapy. • Use of any investigational or non-registered product (drug or vaccine) within the past 30 days before study start and during study. • Psychiatric or addictive disorders of the patient that may compromise his/her ability to give informed consent or to comply with the trial procedures. • Significant dental/oral disease, including prior history or current evidence of osteonecrosis/osteomyelitis of the jaw, or the following: Active dental or jaw condition which requires oral surgery. Non-healed dental/oral surgery. Planned invasive dental procedures for the course of the study. • Relevant immune deficiencies or relevant autoimmune disease, as assessed by the investigator. • Other malignancies within the past three years which need treatment except basal or squamous skin carcinomas or carcinoma in situ of the cervix • Serious cardiac, gastrointestinal, hepatic or pulmonary disease • Patients with serious intercurrent illness, requiring hospitalization. • Other serious illnesses, e.g., serious infections requiring intravenous antibiotics or bleeding disorders. • Hypersensitivity to the active substances of study treatment or to any of the excipients (calcium, vitamin D) • Hereditary fructose intolerance • Women of childbearing potential: Refusal or inability to use highly effective means of contraception • For female patients: the patient is pregnant or lactating or planning to become pregnant within 5 months after the end of the treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This phase IV study aims to investigate possible immunologic and biologic effects of the concurrent administration of PD-1 blocking antibodies and denosumab as primary endpoint. ;Secondary Objective: Not applicable.;Primary end point(s): 1) Dynamic changes of the numbers of central memory, effector memory and/or effector T-cells in the circulating blood (based on expression of CD45RA, CD45RO, CCR7, CD62L, and TCF-1) 2) Dynamic changes of the numbers of cytokine and chemokine present in circulating blood. ;Timepoint(s) of evaluation of this end point: Variables will be determined at baseline, and after 4, 12 and 24 weeks of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety Occurrence of adverse events as assessed by NCI CTC-AE criteria version 5.0 • Efficacy ;Timepoint(s) of evaluation of this end point: 1) Overall response rate at 12 and 24 weeks as determined by RECIST 1.1 criteria 2) Response rate of bone metastases after 12 and 24 weeks of treatment (size and number) as determined by RECIST 1.1 and bone scans | — |
Countries
Germany
Contacts
Public ContactUniversitätsklinik für Dermatologie
Johannes Wesling Klinikum Minden
Outcome results
None listed