A Study to Determine the Safety, Tolerability, Pharmacokinetics and Dynamic Effects of Different Doses of the Study Drug EMD 525797 in Prostate Cancer
Condition: Prostate Cancer; Bone Metastases
MeSH terms: Prostatic Neoplasms
Intervention: EMD 525797
Intervention description: Subjects will be administered with 250 milligram (mg), 500 mg, 1000 mg or 1500 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who will be clinically benefitted at the end of week 6 were continued at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject is no longer benefitted from the treatment as per Investigator's discretion.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Safety; tolerability; pharmacokinetics; pharmacodynamics of EMD 525797; prostate cancer patients

Summary:

      This study is intended to test an experimental new drug called, EMD 525797 (Study Drug). This
      drug is not yet approved for sale and has only been tested in a small number of people to
      date (prior to this study starting another research study was carried out involving 37
      healthy volunteers receiving the Study Drug). Until more is known about this Study Drug, it
      can only be used in research studies.

      This research study is planned to answer important questions about how the Study Drug is
      tolerated and how it may work in patients with prostate cancer with bone metastases.

      This is a small study which is expected to include 24 patients, and will be conducted in
      approximately 3 hospitals in Germany and 1 hospital in Brussels, Belgium. The study will last
      until the last patient has had their last study visit which is expected to be about 18 months
      in total.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of signed written informed consent

          -  Age superior or equal to 18 years

          -  Subjects with histological or cytologically proven prostate cancer with evidence of
             bone metastases on bone scans or CT / MRI after prior chemotherapy with e.g. taxane or
             mitoxantrone Patients should have undergone bilateral orchiectomy or should be on
             continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist
             or antagonist and should have stopped any anti-androgen therapy for at least 4 weeks
             before inclusion in the study. Patients should be either on stable (i.e., since at
             least 3 months) ongoing therapy with a bisphosphonate or without any bisphosphonate
             therapy. Initiation of a bisphosphonate therapy within this time period prior the
             study or during the study is not allowed. Total serum testosterone should be less than
             50 ng/dL or 1.7 nmol/L.

          -  Evidence of progressive disease, defined by at least two PSA values above the
             individual nadir level with an increase of at least 10% each determined at a minimum
             interval of 2 weeks before screening examination. Presence of a measurable lesion is
             not required for study entry. Nodal (in lymph nodes superior or equal to 2cm) or
             visceral progression is sufficient for trial entry independent of PSA.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at study entry
             and an estimated life expectancy of at least 3 months.

          -  Adequate hematological function, defined by white blood cell count (WBC) greater than
             or equal to 3 x 109/L with absolute neutrophil count (ANC) greater than or equal to
             1.5 x 109/L, and lymphocyte count greater than or equal to 0.5 x 109/L; platelet count
             greater than or equal to 100 x 109/L; and hemoglobin greater than or equal to 9 g/dL.

          -  Adequate hepatic function defined by total bilirubin level less than or equal to 1.5
             times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and
             alanine aminotransferase (ALT) levels less than or equal to 2.5 x ULN; or, for
             subjects with documented metastatic disease to the liver, AST and ALT levels less than
             or equal to 5 x ULN.

          -  Adequate renal function defined by serum creatinine less than 1.5 mg/dL.

          -  Effective contraception. If the risk of conception exists, pregnancy has to be avoided
             during the study (SCR to EOS) as well as during at least 3 month after last dosing
             using an effective contraception method (e.g. double barrier method)

        Exclusion Criteria:

          -  Any systemic cytotoxic cancer treatment within 4 weeks before treatment with EMD
             525797.

          -  Acute pathologic fracture, spinal cord progression, hypercalcemia (within 4 weeks
             period prior to screening).

          -  Radiotherapy to bone lesions, orthopaedic surgery, or any investigational drug in the
             30 days before the start of treatment in this study and during treatment period,
             and/or biopsies involving bone within 2 weeks before the start of treatment in this
             study.

          -  Supraphysiologic doses of steroids (defined as superior or equal to 7.5 mg of
             prednisone equivalents per day).

          -  Previous treatment with anti-integrin therapy.

          -  Confirmed or clinically suspected brain metastases.

          -  Known hypersensitivity reactions to any of the components of the study medication.

          -  History of allergic reactions to other monoclonal antibody (mAb) therapy.

          -  Uncontrolled hypertension (systolic greater or equal to 160 mmHg, diastolic greater
             than or equal to 100 mmHg).

          -  Current history of chronic daily aspirin therapy (ASS at doses inferior or equal to
             100 mg is permitted), bleeding disorders and/or history of thromboembolic events
             (history of superficial thrombophlebitis is not an exclusion criterion); thrombolytics
             or oral or parenteral anticoagulants within 10 days prior to study start and during
             treatment period.

          -  Severe peripheral vascular disease or ulceration.

          -  Unstable angina pectoris, or myocardial infarction within 6 months before start of
             study treatment, clinical significant abnormal ECG at screening

          -  Known alcohol or drug abuse.

          -  Participation in another clinical trial within the past 30 days before start of study
             treatment.

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent.

          -  Ongoing uncontrolled infections, including active or chronic hepatitis B or C, ongoing
             HIV infection.

          -  Legal incapacity or limited legal capacity.

          -  All other significant diseases which, in the opinion of the Investigator, might impair
             the subject's tolerance of study treatment.