E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) |
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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 | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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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 | 10029514 |
E.1.2 | Term | Non-small cell lung cancer NOS |
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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 | 10029515 |
E.1.2 | Term | Non-small cell lung cancer recurrent |
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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 | 10029516 |
E.1.2 | Term | Non-small cell lung cancer stage 0 |
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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 | 10029517 |
E.1.2 | Term | Non-small cell lung cancer stage I |
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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 | 10029518 |
E.1.2 | Term | Non-small cell lung cancer stage II |
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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 | 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 | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
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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 | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029515 |
E.1.2 | Term | Non-small cell lung cancer recurrent |
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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 determine the efficacy of 0.10 mg/kg and 0.25 mg/kg ABT-869 using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and to establish the safety/tolerability profile of ABT-869 in subjects with advanced or metastatic NSCLC. |
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E.2.2 | Secondary objectives of the trial |
To identify potential biomarkers that correlate and/or predict efficacy and toxicity in subjects with advanced or metastatic NSCLC and to explore if there are any ethnic differences in tumor response to ABT-869 between Asian and non-Asian NSCLC populations. The tertiary objectives of this study are to assess additional efficacy endpoints such as quality of life, changes in weight and performance status. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
At selected clinical study sites, an optional pharmacogenetic sample collection will be performed. For subjects that have signed the appropriate Informed Consent From, DNA samples from this protocol may be used to assess the influence of genetic variants on pharmacokinetics, safety or efficacy. For example, polymorphisms in genes that encode drug metabolizing enzymes (such as cytochromes or uridine glucuronosyltransferases) or drug transport proteins (such as ATP-binding cassette or solute-linked carrier proteins) may be assessed for their influence on ABT-869 pharmacokinetics. Genetic variants of potential ABT-869 targets (such as VEGF or PDGF RTKs) may also be assessed.
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E.3 | Principal inclusion criteria |
1. Subject must be ≥ 18 years of age. 2. Subject must be histologically or cytologically diagnosed with locally advanced or metastatic NSCLC. 3. Subjects must have at least one lesion measurable by CT scan as defined by RECIST. The measurable lesion may have not received radiation therapy. 4. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. 5. Subject has received at least one prior line of systemic treatment but no more than two treatment regimens for locally advanced or metastatic NSCLC not amenable to cure. 6. Subject must have the following laboratory values: ● Total Bilirubin ≤ 1.5 × upper normal limit (ULN) ● AST/ALT ≤ 2.5 × ULN or ≤ 5.0 ULN if subject has liver metastasis ● PTT ≤ 1.5 × ULN and INR ≤ 1.5 ● ANC ≥ 1.0 × 109/L ● Platelet count ≥ 75 × 109/L ● Creatinine ≤ 1.5 × ULN 7. No other active malignancy within the past 5 years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. 8. Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to two months following completion of therapy. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to initiation of treatment and/or post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. ● Total abstinence from sexual intercourse (minimum one complete menstrual cycle) ● A vasectomized partner ● Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration ● Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream) Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for two months following completion of therapy. 9. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. |
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E.4 | Principal exclusion criteria |
1. Subject has received anti-cancer therapy within 21 days or 5 half lives, whichever is shorter, prior to study drug administration. Anti-cancer therapies include but are not limited to: investigational agents, immunotherapy, anti-cancer traditional Chinese medicine/herbal remedies, hormonal, targeted agents (i.e., erlotinib, imatinib) or biologic therapy. Subject has received cytotoxic chemotherapy (i.e., alkylating agents, microtubule inhibitors, anti-metabolites) within 21 days prior to study drug administration. In addition, subject has not recovered to ≤ Grade 1 clinically significant adverse effects/toxicities of previous therapy. 2. Subject has received radiation or undergone major surgery within the previous 21 days prior to study drug administration. 3. Subject has received targeted VEGF/PDGF TKI (tyrosine kinase inhibitor) therapy (prior Avastin is allowed). 4. Subject has untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study drug administration). 5. History of greater than 10% weight loss during the 6 weeks prior to study entry. 6. Subject has significant central thoracic lesions invading or abutting the heart or major blood vessels with any appreciable cavitation. 7. Subject has clinically relevant hemoptysis described as > 5 ml fresh blood within the last 3 months. Subjects with only flecks of blood in sputum are permitted. 8. The subject has proteinuria CTC Grade > 1 at baseline as measured by a UPC ratio of > 1 and confirmed by a 24 hour urine collection. 9. The subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure > 100 mmHg or systolic blood pressure > 150 mmHg. Subjects may be re-screened if blood pressure is shown to be controlled with or without intervention. 10. The subject has a documented left ventricular ejection fraction < 50%. 11. Subject is receiving therapeutic anticoagulation therapy. Low dose anti-coagulation (e.g., low dose Warfarin) for catheter prophylaxis only will be permitted. No low molecular weight heparin is allowed. 12. Subject is receiving anti-retroviral therapy for HIV. 13. Female subjects who are pregnant or breast-feeding. 14. Clinically significant uncontrolled condition(s) including: ● Active uncontrolled infection ● Class III or IV heart failure as defined by the New York Heart Association functional classification system ● Unstable angina pectoris or cardiac arrhythmia ● Myocardial infarction within last 6 months ● History of adrenal insufficiency ● History of hemorrhagic cerebral vascular accident within last 6 months ● Active ulcerative colitis, Crohn's disease, celiac disease or any other conditions that interfere with absorption ● History of autoimmune disease that has kidney involvement ● History of overt bleeding (> 30 mL bleeding/episode) within 3 months of study drug administration ● Psychiatric illness/social situation that would limit compliance with study requirements ● Any other medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Determine the efficacy of low and high dosages using RECIST and establish safety and tolerability of ABT-869 in NSCLC. |
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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 | No |
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) | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Option for patients in low dose group 0.10 mg/kg of ABT-869 to cross-over to 0.25 mg/kg dose |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Different dose of the same IMP |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 20 |
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 is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |