A clinical study in prostate cancer using a monoclonal antibody

• Register: EUCTR
• Last refreshed on: 8 December 2014
• Main ID: EUCTR2010-021529-11-NL
• Date of registration: 03/02/2011
• Prospective Registration: Yes
• Primary sponsor: Merck KGaA
• Public title: A clinical study in prostate cancer using a monoclonal antibody
• Scientific title: A randomized, double-blind, placebo-controlled, multicenter Phase II trial investigating two doses of EMD 525797 in subjects with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (mCRPC). - PERSEUS
• Date of first enrolment: 21/04/2011
• Target sample size: 165
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021529-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Cross over for placebo group allowed after progression. If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Canada, Germany, Netherlands, Russian Federation, Slovakia, South Africa, Spain, United States

Contacts

• Name: Communication Centre Merck KGaA
• Affiliation: Merck KGaA

• Name: Communication Centre Merck KGaA
• Affiliation: Merck KGaA

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects with asymptomatic or mildly symptomatic mCRPC with progression of bone metastasis (new bone lesion(s)) by bone scan within 4 weeks (28 days) prior to randomization will be eligible for this trial. Subjects must fulfill ALL of the following inclusion criteria:
1. Signed and dated written informed consent prior to any specific trial procedure.
2. Age =18 years, male.
3. Histologically or cytologically confirmed adenocarcinoma of the prostate (Gleason score).
4. Radiological progression of bone lesion(s) with or without soft tissue lesions within 4 weeks (28days) prior to randomization.
5. Stable, ongoing adequate testosterone suppression proven by hypogonadal levels of testosterone (=50 ng/dL) for subjects without surgical castration. Testosterone level will not be documented for subjects who have been surgically castrated.
6. Bisphosphonate treatment has to be initiated at least 2 days prior to start of treatment with EMD 525797.
7. Eastern Cooperative Oncology Group performance status <2.
8. Adequate hematological function: Absolute Neutrophil Count (ANC) =1.5 x 109/L; platelets =100 x 109/L; hemoglobin =9 g/dL (without transfusion).
9. Adequate hepatic function: total bilirubin =1.5 x upper limit of normal (ULN); aspartate transaminase (ASAT) =5 x ULN and alanine aminotransferase (ALAT) =5 x ULN.
10. Creatinine clearance =40 mL /min (calculation based on Cockcroft-Gault formula).
11. International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) within normal range.
12. Effective contraception, e.g., double barrier method, if the risk of conception exists.
13. Ability to comply with the trial and follow-up procedures.
14. Tumor material (from tumor block or punch biopsy) availability must be confirmed at screening. The sample should be collected and sent to the laboratory as soon as possible, ideally by the time of randomization.
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 85

Exclusion criteria:
Subjects are not eligible for this trial if they meet any of the following exclusion criteria:
1. Acute pathologic fracture, spinal cord compression, or hypercalcemia at Screening.
2. Nonsteroidal antiandrogens, e.g., flutamide and bicalutamide, within 30 days before treatment.
3. Chronic and ongoing treatment with opioids (treatment >10 days).
4. Prior chemotherapy, biologic therapy (targeted therapy), or
any experimental therapy for mCRPC.
5. Radiotherapy to bone lesions and/or orthopedic surgery for pathologic fractures. Any kinds of major elective surgery within 30 days prior to trial treatment.
6. Chronic supraphysiologic doses of oral steroids, defined as >10 mg of prednisone equivalents per day.
7. Confirmed or clinically suspected brain metastases.
8. Visceral metastasis.
9. Known hypersensitivity reactions to any of the excipients of the trial medication.
10. History of allergic reactions to any other monoclonal antibody therapy.
11. Uncontrolled hypertension defined as systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg under resting conditions for at least 5 minutes.
12. Chronic daily acetylsalicylic acid (ASS) therapy at doses >100 mg.
13. Bleeding disorders and/or history of thromboembolic events (history of superficial thrombophlebitis is not an exclusion criterion).
14. Treatment with thrombolytics or oral or parenteral anticoagulants within 10 days prior to trial treatment.
15. Severe peripheral vascular disease or ulceration; unstable angina pectoris, or myocardial infarction within 6 months before start of trial treatment, clinically significant abnormal electrocardiogram (ECG) at screening.
16. Known alcohol or drug abuse.
17. Participation in another clinical trial within 30 days before start of trial treatment.
18. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
19. Hepatitis B or C, human immunodeficiency virus (HIV) infection, active or chronic.
20. Legal incapacity or limited legal capacity.
21. All other significant diseases which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment.
22. Other malignancy if treatment has not been completed within 2 years before start of trial treatment.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

subjects with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (mCRPC)
MedDRA version: 14.1 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: DI17E6
Product Code: EMD 525797
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
Current Sponsor code: EMD525797
Other descriptive name: DI17E6
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10.0-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary endpoint of the trial is PFS defined as the time from the date of randomization until the first documented sign of objective radiographic disease progression or death from any cause.
Objective radiographic disease progression is defined as one of the
following conditions:
- Bone lesion progression (appearance of 2 or more new bone lesions compared to baseline) assessed with bone scintigraphy, which should be confirmed by bone scintigraphy 6 weeks later if there are no symptoms. Assessments based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 modified according to the Prostate Cancer Working Group 2 (PCWG-2).
- Soft-tissue lesion progression according to RECIST 1.0 assessed with CT scans.
- Presence of skeletal events defined as cord compression or fracture documented via a scheduled or an unscheduled radiographic assessment triggered by increasing pain (needing opioids or radiation) or other signs and/or symptoms at Investigator discretion.

Secondary Objective: To further evaluate the efficacy of EMD 525797
- To further characterize the safety profile of EMD 525797
- To further evaluate the pharmacokinetic (PK) profile of EMD 525797
- To explore the relationship between number and/or changes of numbers of biomarker and the clinical outcome (e.g., primary and secondary endpoints).

Main Objective: The primary objective of the trial is to evaluate the
clinical anti-tumor acitivity of EMD
525797 administered as 1-hour intravenous (i.v.)
infusion every 3 weeks in terms
of progression free survival (PFS) time in subjects
with asymptomatic or mildly symptomatic mCRPC.

Timepoint(s) of evaluation of this end point: last subject
randomized + 3 months

Secondary Outcome(s)

Secondary end point(s): - To further evaluate the efficacy of EMD 525797
- To further characterize the safety profile of EMD 525797
- To further evaluate the pharmacokinetic (PK) profile of
EMD 525797

Timepoint(s) of evaluation of this end point: last subject
randomized + 3 months

Secondary ID(s)

2010-021529-11-BE

EMR62242-006

Source(s) of Monetary Support

Merck KGaA