E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary prophylaxis for the treatment of chemotherapy induced thrombocytopenia (CIT) in subjects with Non-Small Cell Lung Cancer (NSCLC) receiving myelosuppressive chemotherapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023780 |
E.1.2 | Term | Large cell lung cancer stage IV |
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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 |
To evaluate the safety of AMG 531 in treating CIT in NSCLC subjects receiving myelosuppressive chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of AMG 531 (dose and schedule) in treating CIT in NSCLC subjects receiving myelosuppressive chemotherapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Disease related: • Histologically or cytologically confirmed locally advanced or metastatic stage IIIB (not amenable to surgery or radiotherapy with a curable intent) or stage IV NSCLC who will be receiving Q21 day gemcitabine / carboplatin or gemcitabine / cisplatin • Life expectancy ≥ 12 weeks at the time of screening • Thrombocytopenia as evidenced by a platelet count < 50 x 109/L during the qualifying cycle of chemotherapy, OR platelet count < 100 x 109/L on Day 22 of the qualifying cycle (for eligibility inclusion: ability to receive the same dose of chemotherapy on study), this criteria ensures that the subject must be dose delayed for platelet recovery • Ability to receive the same dose and schedule of chemotherapy during the first on study treatment cycle as was given in the qualifying cycle (except Day 8 gemcitabine) • ANC > 1,000/µL, Hgb > 9.5 g/dL, and platelet count > 100 x 109/L on Day 1 of the first on study chemotherapy treatment cycle
Demographic • Subject must be ≥ 18 years of age • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance
Laboratory • Adequate liver function; AST and ALT < 3.0 x ULN (except for subjects with liver mets which will be excluded if > 5 x ULN); and serum bilirubin ≤ 1.5 times ULN (except for subjects with a confirmed diagnosis of Gilbert’s Syndrome) • Adequate renal function; serum creatinine < 1.5 x ULN
Ethical • Before any study-specific procedure, the appropriate written informed consent must be obtained |
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E.4 | Principal exclusion criteria |
Disease Related • Receipt of >1 prior systemic chemotherapy regimen • Sepsis, disseminated intravascular coagulation, or any other condition (i.e. ITP, TTP, HUS) that may have exacerbated thrombocytopenia • History of unstable angina, CHF {NYHA >class II, see Appendix F}, uncontrolled hypertension {diastolic>100mmHG}, uncontrolled cardiac arrhythmia, or recent (within 1 year of screening) MI • History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 1 year of screening • History of pulmonary embolism or other venous thrombosis within 1 year of screening (except for catheter-related clots)
Medications • Receipt of any nitrosourea (BCNU, CCNU) or mitomycin-C within 6 weeks of screening • Receipt of any thrombopoietic growth factor or related substance • Receipt of granulocyte macrophage colony stimulating factor (GM-CSF) within the last 4 weeks prior to screening • Receipt of any experimental therapy within 4 weeks prior to screening • Receipt of a bone marrow or peripheral blood stem cell infusion (within 1 year of screening)
General • Pregnant or breastfeeding • Reproductive potential and not using adequate contraceptive precautions in the judgment of the investigator • Hypersensitivity to any recombinant E. Coli-derived product • Inability to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint • The incidence of adverse events (AEs) and the incidence of anti-AMG 531antibody formation by treatment group
Secondary Endpoints: • The incidence of subjects in each treatment group who experience grade 3 or 4 thrombocytopenia (< 50 x 109/L) during the first on study chemotherapy treatment cycle • The incidence of subjects in each treatment group who are administered platelet transfusions during the first on study chemotherapy treatment cycle • The platelet count on Day 22 of the first on study chemotherapy treatment cycle (planned Day 1 of the next cycle) by treatment group • The incidence of subjects in each treatment group that require gemcitabine dose reduction on Day 8 of the first on study chemotherapy treatment cycle • The duration of grade 3 or 4 thrombocytopenia experienced during the first on study chemotherapy treatment cycle by treatment group
Exploratory Endpoints • The number of days required for the platelet count to recover from nadir to 100 x 109/L during the first on study chemotherapy treatment cycle in each treatment group • The number of days between Day 1 of the first on study cycle to recovery of platelet count to 100 x 109/L following the nadir within each treatment group • The total incidence of grade 3 and/or 4 thrombocytopenia in each treatment group during the study • The average duration of grade 3 or 4 thrombocytopenia per cycle for each subject in each treatment group during the study • The average platelet nadir per cycle for each subject in each treatment group during the study • The total incidence of platelet transfusion in each treatment group • The incidence of subjects with chemotherapy dose delay and/or dose reductions in each on study treatment cycle by treatment group • The total incidence of chemotherapy dose delays and/or dose reductions attributable to thrombocytopenia in each treatment group during the study • The total incidence of bleeding events in each treatment group during the study • The total incidence of hospitalization related to thrombocytopenia in each treatment group during the study |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
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 | 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 | No |
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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |