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) whose disease has progressed following one or more chemotherapy regimens.
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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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 assess if the addition of oral ABT-751 at the recommended phase 2 dose (RPTD) of 200mg QD to standard docetaxal can prolong progression free survival (PFS) compared to docetaxal alone in subjects with advanced or metastatic NSCLC. |
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E.2.2 | Secondary objectives of the trial |
To determine overall survival, 12-month survival rate, time to disease progression (TTP), PFS as determined by the investigator, disease control rate, response rate, and duration of response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is ≥ 18 years old. 2. The subject has pathologically (histologically or cytologically) documented NSCLC. 3. The subject has locally advanced (Stage III) NSCLC not amenable to curative surgery or radiotherapy or metastatic (Stage IV) NSCLC. 4. The subject has received only one prior anti-tumor treatment regimen in the advanced (Stage III non-curable or metastatic Stage IV) setting (i.e., study participation must be second-line therapy in the metastatic setting). 5. The subject may have received one additional anti-tumor treatment regimen in the neo-adjuvant or adjuvant setting. 6. The subject has experienced progressive disease either during or following the previous anti-tumor treatment regimen. 7. The subject has the presence of measurable disease by RECIST criteria. 8. Subjects with brain metastases must have had clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 30 days of stable neurologic function and no evidence of CNS disease progression. (Subjects with symptoms of CNS metastasis at Screening must have computed tomography [CT] or magnetic resonance imaging [MRI] scans of the brain prior to study entry that demonstrate no evidence of disease.) 9. The subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2. 10. All anti-tumor therapy must be discontinued at least 3 weeks prior to ABT 751/placebo and docetaxel administration. 11. All adverse events from prior anti-tumor treatment are resolved or stable. 12. The subject's life expectancy is ≥ 3 months. 13. The subject must have adequate hematologic, renal and hepatic function as follows: Hematology: Absolute Neutrophil Count (ANC): ≥2000/mm3 Platelet Count: ≥100,000/mm3 Hemoglobin: ≥ 9.0 g/dL
Renal Function: Creatinine:Creatinine Clearance ≥45 mL/min*
Hepatic Function: Bilirubin: ≤1.5 mg/dL (≤3.0 mg/dL with liver metastasis)** Serum Glutamic-Oxaloacetic Transaminase (SGOT): ≤ 2.5 x ULN (≤ 5.0 x ULN with liver metastasis) Serum Glutamic-Pyruvic Transaminase (SGPT): ≤ 2.5 x ULN (≤ 5.0 x ULN with liver metastasis)
*If calculated creatinine clearance is < 45 mL/min, a 24-hour urine collection for creatinine clearance may be performed. **Subjects with Gilbert's disease may have bilirubin up to 2.5 mg/dL (or 3.0 mg/dL with liver metastasis). 14. Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a serum pregnancy test. 15. All female subjects not surgically sterile or postmenopausal (for at least 1 year) and non-vasectomized male subjects must practice at least one of the following methods of birth control: ● Total abstinence from sexual intercourse during the study (minimum one complete menstrual cycle prior to study start); ● Vasectomized partner; ● Hormonal contraceptives (oral, parenteral, or transdermal) for at least 3 months prior to and during study drug administration; ● Double-barrier method (condoms, contraceptive sponge, or vaginal ring with spermicidal jellies or creams). 16. The subject is amenable to completing the Quality of Life (QoL) questionnaire. 17. The subject has voluntarily signed and dated an informed consent form, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to any non-routine study specific procedures.
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E.4 | Principal exclusion criteria |
1. The subject has NCI CTCAE (version 3.0) neurology category findings (e.g., paresthesia, impaired deep tendon reflexes, or weakness) greater than Grade 1. 2. The subject has a documented allergy to sulfa medications. 3. The subject has glucose-6-phosphate dehydrogenase deficiency. 4. The subject has porphyria. 5. The subject has previously received ABT-751 or docetaxel. 6. The subject has received more than one investigational agent for NSCLC as a single agent or part of a previous regimen. (An investigational agent is any drug not currently approved for use in humans. Please contact the Abbott medical monitor with questions regarding investigational agents.) 7. The subject exhibits significant weight loss (≥ 10%) during the 6 weeks before study entry. 8. The subject has a significant history of cardiac, renal, neurologic, psychiatric, endocrinologic, metabolic, or hepatic disease that would adversely affect his/her participating in this study. Questions regarding inclusion of individual subjects should be directed to the Abbott medical monitor. 9. The subject has a current history of a Class 3-4 cardiovascular disability status in accordance with the New York Heart Association Functional Classification. ● Class 3 is defined as marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes fatigue or dyspnea. ● Class 4 is defined as being unable to carry on any physical activity without symptoms and symptoms are present even at rest. Also, if any physical activity is undertaken, symptoms are increased. 10. A female subject who is pregnant or breastfeeding. 11. The subject has previous or current malignancies at other sites, with the exception of: ● adequately treated in situ carcinoma of the cervix uteri; ● basal or squamous cell carcinoma of the skin; ● previous nonpulmonary malignancy (e.g., localized prostate cancer) confined and surgically resected, treated with chemotherapy or radiation therapy, and is considered cured by the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary - 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 | 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 | 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) | No |
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 |
Determine the maximum tolerated dose (MTD) |
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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 | 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) | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 date when the 110th confirmed event of progression occurs or 3 months after the last patient enrolled, whichever comes later, will define completion of the 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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |