E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castrate-Resistant Prostate Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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 is to determine the composite response (measured by change from baseline in skeletal lesions, extra-skeletal lesions, and PSA values) in subjects with metastatic CRPC who receive single-agent 15 mg/kg CNTO 888 IV formulation, administered as a 90-minute infusion once every 2 weeks. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate further clinical and additional biological activity of single-agent CNTO 888 in subjects with metastatic CRPC, including the following endpoints:
• Objective response rate (complete response [CR] +PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
• Progression-free survival (PFS)
• Overall survival (OS)
• PSA response
• Urinary crosslinked N-telopeptide of type I collagen (NTX) response
• Pain response
• Safety profile
• Biological activity (defined by changes in macrophage infiltration, monocyte subsets M1/M2, CCL2 levels in tumor, blood, and serum and urinary bone markers)
• Pharmacokinetics
• Pharmacodynamics
• Antibodies to CNTO 888 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Potential subjects must satisfy all of the following criteria to be enrolled in the study:
• Male age ≥ 18 years
• Sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Histological documentation of adenocarcinoma of the prostate
• Received at least 1 but no more than 2 prior docetaxel-based chemotherapy regimens and had disease progression following the last therapy. Disease progression is defined as:
– Serum PSA progression, defined as a rise in at least 2 consecutive serum PSA values, each obtained at least 1 week apart, and within 4 weeks prior to first dose of study agent (see Attachment 4)
OR
– Radiologic disease progression: If disease progression is shown by bone scan only, then disease progression is defined by the appearance of 2 or more new bone lesions
• Serum PSA ≥ 5.0 ng/mL within 4 weeks prior to the first dose of study agent
• Orchiectomy or testosterone < 50 ng/dL by means of pharmacological/chemical castration within 4 weeks prior to the first dose of study agent
• At least 6 weeks from prior docetaxel chemotherapy regimen to first dose of study agent
• ECOG performance status score of ≤ 2 (see Attachment 3)
• Adequate bone marrow, liver, and renal function within 2 weeks prior to the first dose of study agent as described below:
– Hemoglobin ≥ 9.0 g/dL (5.6 mmol/L; 90 g/L) without transfusion dependency or erythropoiesis-stimulating agents
– Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (1000/mm3) without hematopoietic cytokine support
– Platelets ≥ 100 x 109/L (100,000/mm3) without transfusion dependency or hematopoietic cytokine support
– Coagulation prothrombin time (PT) or international normalized ratio (INR), and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
– AST and ALT ≤ 3 x ULN if no liver metastasis; ≤ 5 x ULN with liver metastasis
– Total bilirubin ≤ 1.5 x ULN
– Serum creatinine ≤ 1.5 x ULN
• Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 6 months after receiving the last dose of study drug.
• Willing/able to adhere to the prohibitions and restrictions specified in this protocol
• To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the clinical study. |
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study:
• Experiences a hormonal treatment withdrawal response (including a lowering of PSA that was previously rising or symptomatic improvement)
• Known or symptomatic CNS metastases
• Residual toxicities resulting from previous therapy that are ≥ Grade 2 (except for alopecia)
• Known allergies, hypersensitivity, or intolerance to CNTO 888 or its excipients (refer to Section 14.1, Physical Description of Study Drug) or clinically significant reactions to chimeric or human proteins
• Vaccinated with live, attenuated vaccines within 4 weeks prior to the first dose of study agent. Inactivated, injectable or inhaled influenza vaccine is permitted
• Bleeding diathesis
• Requires concurrent therapeutic dose of anticoagulation (low-dose prophylaxis is permitted)
• Bisphosphonate therapy initiated < 6 weeks prior to the first dose of study agent or that required dose adjustment during this time
• Treatment with systemic cancer therapy, herbal treatments, over-the-counter treatments for prostate cancer, or local radiotherapy within 4 weeks prior to the first dose of study agent
– Palliative radiotherapy (eg, for pain, fracture prevention) to control a small area of metastatic bone disease may be permitted if the subject has recovered from the effects of the radiotherapy
• Received an investigational drug/agent (including vaccines) or used an investigational medical device within 4 weeks prior to the first dose of study agent or are currently enrolled in an investigational study
• Concomitant treatment such as, immunotherapy, biotherapy, radiotherapy, chemotherapy, investigative therapy, or new steroid therapy (except for topical or inhaled steroids, or unless clinically indicated [eg, for asthmatic attacks, reactions to IV contrast, allergic reactions that develop during the study, severe nausea, vomiting]). The following exceptions apply:
– Subjects on stable doses of steroids for treatment of noncancerous conditions will be allowed to continue on the steroid therapy during the study only if maintained at the same dose (ie, the dose may not be increased during this study).
– Luteinizing Hormone Releasing Hormone (LHRH) is permitted provided the subject is on a stable dose prior to screening
• Prior use of radionucleotide therapy (eg, Strontium89, Samarium)
• Use of disallowed therapies: Non-steroidal antiandrogens (flutamide, bicalutamide, or nilutamide) or other hormonal treatments (such as estramustine or ketoconazole), within 6 weeks prior to the first dose of study agent or as concomitant medication
• Requires transfusion of blood products to meet eligibility criteria, or within 4 weeks prior to the collection of screening hematology laboratory sample
• Uncontrolled infection, clinically important active infection within 4 weeks prior to the first dose of study agent, or currently receiving treatment for an infection
• Major surgery within 4 weeks prior to the first dose of study agent, or planning to have surgery (except for minor surgical procedures) during the study, or planned major surgery within 8 weeks after the last dose of study agent
• Serious concurrent illness (medical or psychiatric), altered mental status (eg, dementia) or any uncontrolled medical condition (eg, uncontrolled diabetes), including the presence of laboratory abnormalities, that places the subject at unacceptable risk by participating in the study, limits full compliance, or confounds the ability to interpret data from the study
• Active angina pectoris or New York Heart Association (NYHA) Class III or IV heart disease. Significant cardiac disease characterized by significant ischemic coronary disease, significant arrhythmias, or congestive heart failure (greater than or equal to NYHA Class II) or myocardial infarction within 6 months prior to the first dose of study agent (see Attachment 6)
• Known to be seropositive for HIV, or known active hepatitis A, B, or C infection
• Transplanted solid organ and receiving immunosuppressive therapy (with the exception of a corneal transplant that was performed ≥ 12 weeks prior to screening)
• Active or symptomatic autoimmune disorders or requiring treatment within the last 5 years (eg, rheumatoid arthritis, Crohn’s disease, systemic lupus, or multiple sclerosis)
• Prior or concomitant malignancy (other than prostate cancer) except adequately treated basal cell or squamous cell carcinoma of the skin, or other cancer for which the subject has been disease-free for ≥ 5 years
• Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the composite response rate, measured by change from baseline in skeletal lesions, extra-skeletal lesions, and PSA values. The composite response rate will be estimated and its 2-sided exact 95% confidence interval will be computed. A subject has a composite response if 1 of the following responses occurs after the first dose of study agent:
• CR or PR according to RECIST criteria
• PSA response at 12 weeks and the absence of skeletal and extra-skeletal progression
• Stable disease at 24 weeks defined as the absence of PSA, skeletal, or extra-skeletal progression |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 |
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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 | No |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | Information not present in EudraCT |
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 |
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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 end of study is defined as the last study assessment for the last subject on study. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 9 |