E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIb/IV Non-Small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small 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 |
Part 1 (Phase 1b): To determine the maximum tolerated dose up to a target dose of 15 mg/kg of AMG 655 that can be administered in combination with paclitaxel/carboplatin
Part 2 (Phase 2): To estimate the efficacy of AMG 655 as assessed by progression free survival time (at two doses selected in part 1) in combination with paclitaxel/carboplatin |
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E.2.2 | Secondary objectives of the trial |
Part 1: To evaluate the safety and tolerability of escalating doses of AMG 655 in combination with paclitaxel/carboplatin To evaluate parameters of clinical benefit as measured by objective response rate, duration of response, time-to-response, progression-free survival and overall survival To evaluate the pharmacokinetics of AMG 655 To evaluate anti-AMG 655 antibody formation
Part 2: To estimate the clinical benefit of AMG 655 in combination with paclitaxel/carboplatin as measured by overall objective response rate, duration of response, time-to-response and overall survival To evaluate the safety and tolerability of AMG 655 in combination with paclitaxel/carboplatin To evaluate the pharmacokinetics of AMG 655 To evaluate anti-AMG 655 antibody formation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Disease Related
• Histologically or cytologically confirmed non-small cell lung cancer. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the subject will be ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy. • Subjects must have advanced non-small cell lung cancer defined as stage IIIB with malignant pleural effusion or stage IV or recurrent disease (recurrent disease is defined as documented disease progression following complete surgical resection for stage I or II disease). Subjects with non-measurable but evaluable disease can be included in the study • Planning to receive up to 6 cycles of chemotherapy • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
Demographic
• Men or women ≥ 18 years of age
Ethical
• Before any study specific procedure is performed, the appropriate approved written informed consent must be obtained
Laboratory
The following results must be obtained within 7 days before enrollment/randomization unless indicated otherwise: • Hematological function as follows: − Hemoglobin ≥ 9 g/dL − Absolute neutrophil count ≥ 1.5 x 109/L − Platelet count ≥ 100 x 109/L (without a transfusion ≤ 14 days prior to enrollment or randomization) • Renal function, as follows: − Calculated creatinine clearance ≥ 40 mL/minute • Hepatic function, as follows: − Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN OR AST or ALT ≤ 5.0 x ULN if clearly attributable to liver metastasis − Total bilirubin ≤ 1.5 x ULN − Alkaline phosphatase ≤ 2.0 x ULN OR alkaline phosphatase ≤ 5 x ULN if liver or bone metastases are present • Partial thromboplastin (PTT) ≤ 1.2 x ULN and international normalized ratio (INR) ≤ 1.5, unless subject is on anti-coagulation therapy. Subjects on therapeutic anticoagulation are eligible if there is no bleeding and they are on a stable dose of anticoagulation therapy (eg, on warfarin with an INR of 2 to 3) for at least 14 days before enrollment/randomization • Amylase ≤ 2 x ULN • Lipase ≤ 2 x ULN
General • Plan to begin protocol specific therapy ≤ 7 days prior to enrollment/randomization |
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E.4 | Principal exclusion criteria |
Disease Related
• Untreated or symptomatic central nervous system metastases. − Subjects with a history of CNS metastases that are both definitively treated and stably controlled are eligible if all of the following apply: 1)definitive therapy has been administered (surgery and/or radiation therapy); 2) there is no additional treatment planned for brain metastases; 3) the subject is clinically stable; 4) the subject is off corticosteroids or on a stable dose of corticosteroids for at least 14 days prior to enrollment/randomization• • Prior chemotherapy as follows: − Any prior chemotherapy for advanced non-small cell lung cancer − Any prior adjuvant or neo-adjuvant chemotherapy for non-small cell lung cancer ≤ 52 weeks prior to enrollment/randomization. Adjuvant or neoadjuvant chemotherapy completed > 52 weeks prior to randomization is permitted. − Any prior chemoradiation for non-small cell lung cancer. • Central (chest) radiation therapy ≤ 28 days prior to randomization, radiation therapy for peripheral lesions ≤ 14 days prior to enrollment/randomization • A history of other malignancies (except: curatively treated non-melanoma skin cancer, in-situ cancer of the cervix, or other in situ cancer with similarly favorable prognosis) unless treated with curative intent, with no treatment administered and without evidence of disease for ≥ 3 years • Other abnormal medical conditions • Documented myocardial infarction or unstable/uncontrolled cardiac condition (eg, unstable angina, congestive heart failure [New York Heart Association > Class II]) ≤ 52 weeks prior to enrollment/randomization • History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders ≤ 28 days prior to enrollment/randomization • History of any medical or psychiatric condition or addictive disorder, or laboratory abnormality that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results • Major surgical procedure ≤ 30 days prior to enrollment/randomization or not yet recovered from prior major surgery • Minor surgical procedure ≤ 7 days prior to enrollment/randomization or not yet recovered from prior minor surgery • Known positive test for human immunodeficiency virus, hepatitis C virus or acute or chronic hepatitis B infection • Any co-morbid disease that would increase the risk of toxicity
Medications and other treatments
• Currently treated or previously treated with biologic, small molecule, immunotherapy, or other agents to treat advanced non-small cell lung cancer • Recent infection requiring a course of systemic anti-infectives that was completed ≤ 7 days before enrollment/randomization (with the exception of uncomplicated urinary tract infection) • Yellow fever vaccination within 30 days of randomization
General
• Subject is not able to tolerate intravenous drug infusions • Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s) • Subject of child-bearing potential is evidently pregnant or is breast feeding • Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 3 months after the last study drug administration for women, and 6 months for men • Subject has known sensitivity to any of the products to be administered during the study • Subject was previously enrolled/randomized in this study • Subject will not be available for follow-up assessment • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures • Subject unwilling or unable to comply with study requirements |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: The incidence of adverse events and clinical laboratory abnormalities defined as dose limiting toxicities
Part 2: Progression free survival |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 7 |
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 | 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 | No |
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 will occur when all subjects have died, completed the treatment period or long-term follow-up (up until 36 months from the date that the last subject was randomized), whichever is later. The end of study for a subject is defined as 36 months from the last subject randomized or death, whichever occurs first. The end of study visit for a subject is planned for approximately 60 days after a subject discontinues investigational product administration. |
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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 | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 36 |