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

Prostate Cancer Clinical Trial

Official title:

Phase I, Open-label Study to Investigate Safety, Tolerability, PK, and PD of EMD 525797 After Single and Repeated Dosing at Different Dose Levels in Subjects With Hormone-resistant Prostate Cancer With Bone Mets and Progressive Disease Following Prior CTX

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00958477
• Other study ID #: EMR62242_002
• Status: Completed
• Phase: Phase 1
• First received: August 11, 2009
• Last updated: July 30, 2014
• Start date: October 2008
• Est. completion date: March 2011

Study information

• Verified date: July 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Paul-Ehrlich-InstitutBelgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of signed written informed consent

2. Age superior or equal to 18 years

3. 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.

4. 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.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at study entry and an estimated life expectancy of at least 3 months.

6. 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.

7. 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.

8. Adequate renal function defined by serum creatinine less than 1.5 mg/dL.

9. 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:

1. Any systemic cytotoxic cancer treatment within 4 weeks before treatment with EMD 525797.

2. Acute pathologic fracture, spinal cord progression, hypercalcemia (within 4 weeks period prior to screening).

3. 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.

4. Supraphysiologic doses of steroids (defined as superior or equal to 7.5 mg of prednisone equivalents per day).

5. Previous treatment with anti-integrin therapy.

6. Confirmed or clinically suspected brain metastases.

7. Known hypersensitivity reactions to any of the components of the study medication.

8. History of allergic reactions to other monoclonal antibody (mAb) therapy.

9. Uncontrolled hypertension (systolic greater or equal to 160 mmHg, diastolic greater than or equal to 100 mmHg).

10. 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.

11. Severe peripheral vascular disease or ulceration.

12. Unstable angina pectoris, or myocardial infarction within 6 months before start of study treatment, clinical significant abnormal ECG at screening

13. Known alcohol or drug abuse.

14. Participation in another clinical trial within the past 30 days before start of study treatment.

15. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.

16. Ongoing uncontrolled infections, including active or chronic hepatitis B or C, ongoing HIV infection.

17. Legal incapacity or limited legal capacity.

18. All other significant diseases which, in the opinion of the Investigator, might impair the subject's tolerance of study treatment.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Metastases
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• EMD 525797
EMD 525797 will be administered as an i.v. over 1 hour every two weeks for 6 weeks. Subjects with clinical benefit at end of week 6 will be offered continuation of treatment with EMD 525797 at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or in the opinion of the investigator, the subject is no longer benefiting from treatment. Dose escalation carried out as follows: Dose-level 1: 250 mg of EMD 525797 i.v. Dose-level 2: 500 mg dose of EMD 525797 i.v. Dose-level 3: 1000 mg dose of EMD 525797 i.v. Dose-level 4: 1500 mg dose of EMD 525797 i.v.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet - Medical Oncology Clinic	Brussels
Germany	Universitätsklinikum Aachen, AÖR - Medizinische Fakultät der RWTH - Klinik für Urologie	Aachen
Germany	Universitätsklinikum "Carl Gustav Carus" Dresden - Klinik und Poliklinik für Urologie	Dresden
Germany	Klinikum Rechts der Isar - Urologische Klinik und Poliklinik	München

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Belgium,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of dose limiting toxicity during the first 6 weeks of treatment		6 weeks	Yes
Primary	Total number of adverse events and total number of serious adverse events		6 weeks	Yes
Secondary	PD Serum levels of anti-EMD 525797 antibodies to characterize the immunogenic potential		Up to week 7	No
Secondary	PD IL8/6		Up to week 7	No
Secondary	PD C-Reactive		Up to week 7	No