A Study to Determine the Safety, Tolerability, Pharmacokinetics and Dynamic Effects of Different Doses of the Study Drug EMD 525797 in Prostate Cancer

NCT00958477 | Completed Phase 1 Results

• 1 other identifier: EMR62242_002
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

Prostate Cancer; Bone Metastases

Keywords

Safety; tolerability; pharmacokinetics; pharmacodynamics of EMD 525797; prostate cancer patients

Outcome Measures

Primary Outcomes (10)

• Number of Subjects With Dose Limiting Toxicity (DLT)

  DLT was defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 as any Grade 3 or 4 hematological or non-hematological toxicity occurring at any dose level until the end of Week 6, and suspected to be reasonably related to the investigational product by the Investigator and/or Sponsor except for allergic/ hypersensitivity reactions and any Grade 3/4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days.

  Baseline up to 6 weeks

• Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs

  An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.Treatment-related are events which had causal relationship to study drug as assessed by the Investigator and were suspected to be reasonably related to the study drug.

  Baseline up to 534 days

• Observed Maximum Serum Concentration (Cmax) of EMD 525797 After First Infusion

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 1

• Observed Maximum Serum Concentration (Cmax) of EMD 525797 After Third Infusion

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 5

• Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Infusion

  Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log linear trapezoidal rule.

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 1

• Total Body Clearance of Drug From Serum (CL) After First Infusion

  Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Total body clearance of drug from serum, calculated as CL = dose/AUC0-inf. Where AUC0-inf is area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above lower limit of quantification (LLQ) and λz is elimination rate constant.

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 1

• Apparent Volume of Distribution During Terminal Phase (Vz) of EMD 525797 After First Infusion

  Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as = Dose/(AUC0-inf \*λz) after first infusion. Where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Where AUC0-inf is area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above lower limit of quantification (LLQ) and λz is elimination rate constant.

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 1

• Trough Serum Concentration (Ctrough) Of EMD 525797 at Week 1

  Ctrough is the concentration prior to study drug administration.

  pre-dose at Week 1

• Trough Serum Concentration (Ctrough) Of EMD 525797 at Week 3

  Ctrough is the concentration prior to study drug administration.

  pre-dose at Week 3

• Trough Serum Concentration (Ctrough) Of EMD 525797 at Week 5

  Ctrough is the concentration prior to study drug administration.

  pre-dose at Week 5

Secondary Outcomes (25)

• Time to Reach Observed Serum Concentration (Tmax) After First Infusion

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 1

• Time to Reach Observed Serum Concentration (Tmax) After Third Infusion

  pre-dose, end of infusion, 4, 8, 24, 48, 96, 168 and 336 hours post-infusion at Week 5

• Number of Subjects With Positive Anti-EMD 525797 Antibodies

  Week 1, 3, 5, 8, 9

• Serum Levels of Interleukin 6 (IL-6) and Interleukin 8 (IL-8)

  Week 1 up to a maximum of 56 days

• C-Reactive Protein Levels

  Week 1 up to a maximum of 56 days

Study Arms (1)

EMD 525797

EXPERIMENTAL

Biological: EMD 525797

Interventions

EMD 525797 BIOLOGICAL

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.

EMD 525797

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed written informed consent
• Age superior or equal to 18 years
• 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)

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (4)

Institut Jules Bordet - Medical Oncology Clinic

Brussels, Belgium

Location

Universitätsklinikum Aachen, AÖR - Medizinische Fakultät der RWTH - Klinik für Urologie

Aachen, Germany

Location

Universitätsklinikum "Carl Gustav Carus" Dresden - Klinik und Poliklinik für Urologie

Dresden, Germany

Location

Klinikum Rechts der Isar - Urologische Klinik und Poliklinik

München, Germany

Location

Related Publications (1)

• Wirth M, Heidenreich A, Gschwend JE, Gil T, Zastrow S, Laniado M, Gerloff J, Zuhlsdorf M, Mordenti G, Uhl W, Lannert H. A multicenter phase 1 study of EMD 525797 (DI17E6), a novel humanized monoclonal antibody targeting alphav integrins, in progressive castration-resistant prostate cancer with bone metastases after chemotherapy. Eur Urol. 2014 May;65(5):897-904. doi: 10.1016/j.eururo.2013.05.051. Epub 2013 Jun 6.

  PMID: 23791392 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abituzumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Wolfgang Uhl, Dr, Dipl. Chem., Physician

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2009
• First Posted: August 13, 2009
• Study Start: October 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: March 1, 2011
• Last Updated: August 2, 2017
• Results First Posted: August 2, 2017

Record last verified: 2017-03

Locations

BE (1); DE (3)