| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Non Small Cell Lung Cancer | |
| MedDRA Classification |
| 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 is to compare maintenance therapy with pemetrexed plus BSC versus placebo plus BSC, in terms of the overall survival time (OS) in patients with Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV NSCLC who have not progressed during four cycles of platinum?based induction chemotherapy. | |
| E.2.2 | Secondary objectives of the trial | The secondary objectives of the study are to compare the following between the randomized treatment arms:
·time-to-event efficacy endpoints:
-progression-free survival time (PFS)
-time to objective progressive disease (TPD)
-time to worsening of symptoms (TWS)
·objective tumor response rate
·adverse events
·changes in individual symptom scores and quality of life using the Lung Cancer Symptom Scale (LCSS)
| |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | [1]Histologic or cytologic diagnosis of NSCLC Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or Stage IV prior to induction therapy. See Attachment JMEN.3, American Joint Committee on Cancer Staging Criteria (Fleming et al. 1997).
[2]Patients must have had one of the following induction therapies for treatment of Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV NSCLC: gemcitabine plus carboplatin, paclitaxel plus carboplatin, or docetaxel plus carboplatin, gemcitabine plus cisplatin, paclitaxel plus cisplatin, or docetaxel plus cisplatin (see Section 5.5 for acceptable doses and schedules).
[3]Patients must have received only one chemotherapeutic doublet lasting precisely four cycles.
[4]Induction regimens must be based on 21-day cycles.
[5]Documented evidence of a tumor response of CR, PR, or SD. Tumor assessment must occur between Cycle 4 (Day 1) of induction therapy and the date of randomization. This response does not have to be confirmed in order for the patient to be randomized. Refer to Section 6.1.1 (and Attachment JMEN.5) for the definition of tumor response (RECIST; Therasse et al. 2000).
Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements for response determination (see Attachment JMEN.5).
[6]ECOG performance status (Oken et al. 1982) of 0 or 1 (see Attachment JMEN.4).
[7]At least 18 years of age.
[8]Adequate organ function, including the following:
·Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ³1.5 ´ 109/L, platelets ³100 ´ 109/L, and hemoglobin ³9 g/dL.
·Hepatic: bilirubin £1.5 times the upper limit of normal (ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) £3.0 ´ ULN (ALP, AST, and ALT £5 ´ ULN are acceptable if the liver has tumor involvement).
·Renal: calculated creatinine clearance (CrCl) ³45 mL/min based on the standard Cockcroft and Gault formula (Cockcroft and Gault 1976).
[9]Prior radiation therapy allowed to <25% of the bone marrow (Cristy and Eckerman 1987). Prior radiation to the whole pelvis is not allowed.
Prior radiotherapy must be completed at least 4 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment.
[10]Signed informed consent document on file.
[11]Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the study. Women with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
[12]Estimated life expectancy of at least 12 weeks.
[13]Patient compliance and geographic proximity that allow adequate follow up.
[14]Patient must receive on-study therapy no earlier than 21 days and no later than 42 days from their last cycle (Day 1) of induction therapy.
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| E.4 | Principal exclusion criteria | [15]With the exception of those chemotherapies listed as Inclusion criterion [2], patients will be excluded if they have received prior systemic anticancer therapy (including adjuvant early-stage treatment for NSCLC) or any systemic treatment for any other cancer.
[16]Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[17]Inability to comply with protocol or study procedures.
[18]A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient’s ability to complete the study.
[19]A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV (see Attachment JMEN.6).
[20]Central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off of corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography (CT) or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required.
[21]Presence of clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
[22]Concurrent administration of any other antitumor therapy.
[23]Inability to interrupt aspirin or other nonsteroidal anti?inflammatory drugs (NSAIDs) for a 5-day period (8-day period for long?acting agents, such as piroxicam).
[24]Inability or unwillingness to take folic acid or vitamin B12 supplementation.
[25]Inability or unwillingness to take corticosteroids.
[26]Received an induction chemotherapy regimen that was not based on a 21-day cycle.
[27]Pregnant or breast feeding.
[28]Have a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Patients with a history of low?grade (Gleason score £6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.
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| E.5 End points |
| E.5.1 | Primary end point(s) | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Information not present in EudraCT |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | | This study will be considered complete following final validation and authorization to “lock” the database (after the survival analysis). With a “locked” database, the study may be closed and further data collection stopped. The Lilly clinical research physician will notify investigators in the event of study closure and the decision to stop collecting data. | |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
