Trial document




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  DRKS00016064

Trial Description

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Title

Evaluation of immunological effects of the RANKL-inhibitor Denosumab when administered concurrently with PD1-blocking antibodies (Nivolumab, Pembrolizumab) in patients with metastatic malignant melanoma with bone involvement

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Trial Acronym

Bonemet

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Evaluation of immunological effects of the RANKL-inhibitor Denosumab when administered concurrently with PD-1-blocking antibodies (Nivolumab or oder Nivolumab + Ipilimumab or Pembrolizumab) in patients with metastatic malignant melanoma with bone involvement.

Protocol amendment 2.0 dated 25 June 2019 adapted the protocol in order to better fit the standard of care:
Most relevant changes are:
• Endpoints have been widened to dynamic changes of cells
• Inclusion and exclusion criteria: adapted to more common medical standards for this indication, for example: inclusion criteria: planned therapy with PD-blocking antibodies opened by adding combination of nivolumab and ipilimumab

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Brief Summary in Scientific Language

Evaluation of immunological effects of the RANKL-inhibitor Denosumab when administered concurrently with PD1-blocking antibodies (Nivolumab or Nivolumab + Ipilimumab or Pembrolizumab) in patients with metastatic malignant melanoma with bone involvement.

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Do you plan to share individual participant data with other researchers?

Yes

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Description IPD sharing plan:

The results of the study will be published in general publications.

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Organizational Data

  •   DRKS00016064
  •   2018/12/13
  •   [---]*
  •   yes
  •   Approved
  •   8062_AMG_M_2018, Ethikkommission der Medizinischen Hochschule Hannover
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Secondary IDs

  •   2016-001925-15 
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Health Condition or Problem studied

  •   C43.9 -  Malignant neoplasm: Malignant melanoma of skin, unspecified
  •   C79.5 -  Secondary malignant neoplasm of bone and bone marrow
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Interventions/Observational Groups

  •   All patients will receive a PD-1 blocking antibody (nivolumab or nivolumab + ipilimumab or pembrolizumab) and the RANKL inhibitor denosumab.
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Basic research/physiological study
  •   Single (group)
  •   IV
  •   No
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Primary Outcome

1) Dynamic changes of the numbers of central memory, effector memory and/or effector T-cells in 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.
Variables will be determined at baseline, and after 4, 12 and 24 weeks of therapy. The profile over time as well as the time point with the highest difference to baseline will be assessed. The expectation is that the numbers are increasing with increasing duration of therapy.

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Secondary Outcome

• Safety
Occurrence of adverse events as assessed by NCI CTC-AE criteria version 5.0
• Efficacy
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

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2019/04/16
  •   20
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

• Provision of tumor tissue from metastatic site of disease for biomarker analysis and confirmation of diagnosis by central laboratory. 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:
o WBC ≥ 2000/μL
o Neutrophils ≥ 1000/μL
o Platelets ≥ 100 x103/μL
o Hemoglobin ≥ 9.0 g/dL
o Serum creatinine ≤ 2.0 x ULN OR
o Creatinine clearance (CrCl) ≥ 35mL/min (using the Cockcroft-Gault formula)
o AST/ALT ≤ 3 x ULN, in case of liver metastases ≤ 5 x ULN
o Total Bilirubin ≤ 2.0 x ULN (except subjects with Gilbert Syndrome, who may have total bilirubin up to 5 x ULN)
o 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

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Exclusion Criteria

• Prior therapy with CTLA-4-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.

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Addresses

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    • Alcedis GmbH
    • Ms.  Dr.  Elke  Heidrich-Lorsbach 
    • Wincesterstr. 3
    • 35394  Giessen
    • Germany
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    • Skin Cancer Center HannoverDepartment of Dermatology and AllergyHannover Medical School
    • Mr.  Prof. Dr. med.  Ralf  Gutzmer 
    • Carl Neuberg Str.1
    • 30625  Hannover
    • Germany
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    • Alcedis GmbH
    • Ms.  Dr.  Bettina  Storz-Arnold 
    • Wincester Straße 3
    • 35394  Gießen
    • Germany
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Sources of Monetary or Material Support

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    • AMGEN GmbH
    • Ms.  Beate  Mengoni 
    • Riesstraße 24
    • 80992  München
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.