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.
|
|
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 |
|
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 the study, which will be conducted in the US only, is to determine the maximum tolerated dose (MTD) of ABT-751 when administered daily for 14/21 days, in combination with standard pemetrexed (500 mg/m2 every 21 days).The primary objective of the Phase 2 portion of the study (estimated to begin enrollment in Sep-Nov 2006) is to assess the impact on progression-free survival of the combination of ABT-751 + pemetrexed compared to pemetrexed alone in subjects with NSCLC who have received at least one prior chemotherapy regimen. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the Phase 2 portion of the study will be overall survival, response rate, duration of response, time to progression (TTP), quality of life (QoL), and to characterize toxicities associated with ABT-751 when administered in combination with pemetrexed. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years old. 2. The subject has histologically-documented NSCLC. 3. The subject has locally advanced (Stage III) or metastatic (Stage IV) NSCLC not amenable to curative surgery or radiotherapy. 4. The subject has received at least 1 prior treatment regimen for NSCLC in the neo-adjuvant, adjuvant or metastatic setting. 5. The subject has received no more than 2 prior treatment regimens for NSCLC (i.e., study participation must be second-line therapy in the metastatic setting). 6. The subject has received no more than 1 chemotherapy treatment regimen in the metastatic setting. 7. The subject has experienced progressive disease either during or following the previous chemotherapy regimen. 8. The subject exhibits the presence of measurable disease by RECIST criteria. 9. 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.) 10. The subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2. 11. All anti-tumor therapy has been discontinued at least 3 weeks prior to study start administration. 12. All adverse events from prior anti-tumor treatment are resolved or stable. 13. Adequate hematologic, renal and hepatic function: no NYHA Class 3-4 heart failure 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, diaphragm, or vaginal ring with spermicidal jellies or creams). 16. The subject's life expectancy is ≥ 3 months. 17. The subject is amenable to completing the Quality of Life (QoL) questionnaire. 18. 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. |
|
E.4 | Principal exclusion criteria |
1. The subject has greater than Grade 1 NCI CTCAE (Version 3.0) 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 (≥ 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 with no evidence of disease within three years of initiation of study ● previous nonpulmonary malignancy, which has been treated with surgery, chemotherapy, or radiation therapy and is considered cured by the investigator, may be approved by the Abbott Medical Monitor.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis 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. |
|
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) |
|
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 1/2: Open-label, Phase II: double-blind |
|
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 |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
| |
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 | 6 |
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 |