E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
subjects with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (mCRPC) |
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E.1.1.1 | Medical condition in easily understood language |
subjects with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (mCRPC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to evaluate the clinical anti-tumor activity 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. |
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E.2.2 | Secondary objectives of the trial |
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). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with asymptomatic or mildly symptomatic mCRPC with progression of bone metastasis (new bone lesion(s)) by bone scan within 42 days prior to Screening 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
last subject
randomized + 3 months |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
last subject
randomized + 3 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Cross over for placebo group allowed after progression. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Russian Federation |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The cut-off date for analysis of the primary endpoint will be defined as the time:
- when the planned number of events was reached (i.e., 110 subjects died or progressed per PFS definition) or not later than 3 months after the date of the last subject´s randomization.
(for more details see section 5.7 in the clinical study protocol).
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |