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 chemotherapy regimen in the advanced setting.
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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 |
The primary objective of the Phase 1 portion of this study (conducted in the U.S. only) is to determine the MTD and RPTD of ABT-751 when administered for 14 consecutive days in a 21 day cycle in combination with standard pemetrexed (500 mg/m2) in subjects with advanced or metastatic NSCLC. The primary objective of the Phase 2 portion of the study is to assess if the addition of ABT-751 at the RPTD to standard pemetrexed can prolong PFS compared to pemetrexed alone in subjects with advanced or metastatic NSCLC. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the Phase 1 portion of this study are to characterize the pharmacokinetics of ABT-751 and pemetrexed, to assess the safety profile of the ABT-751/pemetrexed combination, and to obtain a preliminary assessment of anti-tumor activity in subjects with advanced or metastatic NSCLC. The secondary objectives of the Phase 2 portion of the study will be to determine overall survival, 12-month overall survival rate, time to disease progression (TTP), disease control rate, response rate, and duration of response. The tertiary objectives of Phase 2 include quality of life and performance status assessment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age ³ 18 years old. 2.The subject has pathologically (histologically and/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 disease or metastatic Stage IV) setting (i.e., study participation must be second line therapy in the advanced 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 (Requirement for Phase 2 only). 7.The subject exhibits the presence of measurable disease by RECIST criteria (Requirement for Phase 2 only). 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 0-2. 10.All anti-tumor therapy has been discontinued at least 3 weeks prior to study start administration. 11.All adverse events from prior anti-tumor treatment are resolved or stable. 12.Adequate hematologic, renal and hepatic function 13.Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a serum pregnancy test. 14.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 listed methods of birth control. 15.The subject's life expectancy is ³ 3 months. 16.The subject is amenable to completing the Quality of Life (QoL) questionnaire (Requirement for Phase 2 only). 17.Subject has voluntarily signed and dated an informed consent form, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to any study specific procedures.
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E.4 | Principal exclusion criteria |
1.The subject has greater than Grade 1 NCI CTCAE (Version 3.07) neurology category findings (e.g., paresthesia, deep tendon reflexes, or weakness that is subjective and/or does not interfere with function). 2.The subject has a documented allergy to sulfa medications. 3.The subject has previously received ABT-751 or pemetrexed. 4.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.) 5.The subject exhibits significant weight loss (³ 10%) during the 6 weeks before study entry. 6.The subject has glucose-6-phosphate dehydrogenase deficiency and/or porphyria. 7.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. 8.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. 9.A female subject is pregnant or breastfeeding. 10.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) |
The primary efficacy analysis of the Phase 2 portion of the study will be a comparison of PFS (radiologic progression as determined by the Central Imaging Center, clinical progression as determined by the investigator, or death) distributions between the pemetrexed + ABT-751 and pemetrexed + placebo treatment groups. For a given subject, PFS will be defined as the number of days from the day the subject was randomized to the day the subject experiences a confirmed event of disease progression (radiologic progression as determined by the Central Imaging Center or clinical progression as determined by the investigator) or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression will be included, regardless of whether the event occurred while the subject was still taking study drug or had previously discontinued study drug. All events of death will be included for subjects who had not experienced disease progression provided the death occurred within 42 days of the last tumor assessment, vital sign measurement, performance status assessment, or physical exam, whichever is latest. If the subject does not have a confirmed event of disease progression nor has the subject died, the subject's data will be censored at the date of the subject's last available tumor assessment, vital sign measurement, performance status assessment, or physical exam, whichever is last.
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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) | 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 |
determine the Maximum tolerated dose (MTD) and the recommended Phase II dose (RPTD) |
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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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Phase I: Open-label, Phase II: double-blind |
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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 | Yes |
E.8.2.3 | Other | No |
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 | Information not present in EudraCT |
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 |
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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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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 |