| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Bone metastases of solid tumors (except lung) or multiple myeloma bone disease |
|
| MedDRA Classification |
| 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 |
To determine the effectiveness of AMG 162 in reducing urinary N-telopeptide (uNTx)
below 50 nM BCE / mM creatinine in advanced cancer subjects with bone metastases
(including multiple myeloma subjects with bone disease) with uNTx levels above 50 nM BCE / mM creatinine during intravenous bisphosphonate treatment. |
|
| E.2.2 | Secondary objectives of the trial |
To characterize the safety profile of AMG 162 when administered subcutaneously (SC) at 180 mg every 4 weeks or 180 mg every 12 weeks, as compared with intravenous (IV)
bisphosphonates administered every 4 weeks.
Exploratory objectives:
Treatment phase:
To investigate potential biomarker development by biochemical analysis of urine, serum and plasma.
Extension phase:
-To evaluate the safety of AMG 162 as a long term treatment in advanced cancer subjects with bone metastases (including multiple myeloma subjects with bone disease).
-To determine the effectiveness of AMG 162 in reducing uNTx below 50 nM BCE/mM creatinine.
-To investigate changes from baseline uNTx values over the course of the extension. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Treatment phase inclusion criteria:
-Patients ≥18 years of age with histologically confirmed solid tumor carcinomas
(except lung) or multiple myeloma
- Radiographic evidence (eg MRI, bone scan, CT scan, X-ray, etc) of 1 or more bone lesions. Radiographic evidence of diffuse osteopenia/ osteoporosis (evaluated by DXA scan or X-ray) is acceptable radiographic evidence for multiple myeloma bone disease.
- Currently receiving intravenous bisphosphonates for the treatment of bone metastases as defined in section 4.1.1.3 of protocol.
- Urinary NTx level > 50 nM BCE/mM creatinine in one measurement obtained within 4 weeks before study day 1
- ECOG score (0, 1, or 2)
- Adequate organ function (see section 4.1.1.6 of protocol for definition of criteria)
- Concurrent systemic anti-neoplastic therapy is allowed during study treatment.
There should be no planned change to subject’s anti-neoplastic regimen for 4 weeks prior to first administration of investigational product and for four weeks after first administration of investigational product.
- Before any study-specific procedure, the appropriate informed consent must be
obtained.
Extension Phase Inclusion Criteria:
-Completed the treatment phase and are currently enrolled in AMG 162 study 20040114
-For subjects randomized to the IV bisphosphonate arm during the treatment phase, urinary NTx level >50 nm BCE/mM creatinine in one measurement obtained within 4 weeks of enrollment into the extension phase
-ECOG score (0, 1, or 2)
-Adequate organ function as defined by criteria given in section 4.2.1.4 of protocol.
-Before any study-specific procedure, the appropriate informed consent for the extension phase must be obtained
|
|
| E.4 | Principal exclusion criteria |
Treatment phase exclusion criteria:
-Unresolved toxicities > grade 2 from prior anti-cancer therapy (per investigator judgment), excluding alopecia
-More than two prior SREs
-Known brain metastases
-Prior history of or current evidence of osteonecrosis/ osteomyelitis of the jaw
-Active dental or jaw condition which requires oral surgery
-Non-healed dental/ oral surgery
-Planned invasive dental procedures for the course of the study
-Prior administration of OPG construct (i.e. AMGN-0007, Fc-OPG), or AMG 162
-Administration of calcitonin, parathyroid hormone related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks prior to randomization
-Concomitant chronic systemic corticosteroid administration (> 5 mg/day of prednisone or equivalent), unless the corticosteroids are administered as part of antineoplastic treatment
-Evidence of impending fracture in weight bearing bones
-Radiation therapy to bone within 2 weeks before randomization.
-Autologous transplantation less than one year before randomization
-Prior allogeneic transplantation
-Evidence of any of the conditions per subject self report or medical chart review given under section 4.1.2.15 of the protocol.
-Any organic or psychiatric disorder, serum chemistry, or hematology, which in the opinion of the investigator may prevent the subject from completing the study or interfere with the interpretation of the study results
-Is currently enrolled in the active treatment phase of a study investigating an unapproved product or device, or has been treated within the last 30 days with an unapproved product or device (thalidomide use is allowed). Subjects in the observational phase of clinical studies (eg, to collect survival data) are allowed.
-Pregnancy or breastfeeding as described in section 4.1.2.18
-Known sensitivity to any of the products to be administered during dosing (i.e., bisphosphonates or mammalian derived products)
-Any kind of disorder that compromises subject’s ability to give written informed consent and/or to comply with study procedures
-Patients with urinary tract stents or catheters
Extension phase exclusion criteria:
-For subjects randomized to AMG 162 during the treatment phase only, greater than 25 weeks between last dose of investigational product (AMG 162) and enrollment into extension
-More than two prior SREs
-Known brain metastases
-Prior history of or current evidence of osteonecrosis/ osteomyelitis of the jaw
-Active dental or jaw condition which requires oral surgery
-Non-healed dental/ oral surgery
-Planned invasive dental procedures for the course of the study
-Administration of calcitonin, parathyroid hormone related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks prior to randomization into the extension phase
-Concomitant chronic systemic corticosteroid administration (> 5 mg/day of prednisone or equivalent), unless the corticosteroids are administered as part of antineoplastic treatment
-Evidence of any of conditions per subject self report or medical chart review as listed under section 4.2.2.10 of the protocol
-Any organic or psychiatric disorder, serum chemistry, or hematology, which in the opinion of the investigator may prevent the subject from completing the study or interfere with the interpretation of the study results
-Is currently enrolled in the active treatment phase of a study investigating an unapproved product or device, or has been treated within the last 30 days with an unapproved product or device (Thalidomide use is allowed). Subjects in the observational phase of clinical studies (eg, to collect survival data) are allowed.
-Pregnancy or breastfeeding as described in section 4.2.2.13 of the protocol
-Known sensitivity to any of the products to be administered during dosing (i.e., or mammalian derived products)
-Any kind of disorder that compromises subject’s ability to give written informed consent and/or to comply with study procedures |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the proportion of subjects with urinary N-Telopeptide <50 nM BCE / mM creatinine at week 13. |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
|
| End of study is defined as last formal subject visit (Week 57 for subjects completing treatment phase follow-up but not participating in the extension phase; Extension Week 137 for subjects completing the extension phase follow-up) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
Print
