| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Extensive stage Disease 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 of the study is to compare the overall survival of previously untreated patients with ED-SCLC after treatment with pemetrexed plus carboplatin versus etoposide plus carboplatin. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess and compare the following variables between treatment arms:
• overall survival among a subgroup of patients classified as “sensitive” with respect to the results of a prospectively defined set of biomolecular assays
• time-to-event variables, including:
o objective progression-free survival (PFS)
o survival without Grade 4 toxicity (G4 SWT)
o survival without Grade 3-4 toxicity (G3-4 SWT)
o time to worsening of HRQoL (health-related quality of life) (TWQ)
• objective tumor response
• time-to-event variables and objective tumor response among the subgroup of patients classified as “sensitive” with respect to the results of a prospectively defined set of biomolecular assays
• changes in dimensions of HRQoL
• the safety and adverse event profile (including Common Terminology Criteria for Adverse Events [CTCAE Version 3.0, NCI 2003] grades for laboratory and nonlaboratory adverse events)
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following
criteria:
[1] Histological or cytological diagnosis of ED-SCLC, including malignant pleural effusion (see Protocol Attachment JMHO.4 Staging of Small Cell Carcinoma of Lung).
[2] Performance status of 0 to 2 on the ECOG performance status schedule (Oken et al. 1982). (See Protocol Attachment JMHO.3)
[3] No prior systemic chemotherapy, immunotherapy, or biological therapy for SCLC.
[4] Prior radiation therapy allowed to <25% of the bone marrow. Patients who have received prior radiation to the whole pelvis or chest for the treatment of SCLC are not eligible. Prior radiotherapy must be completed at least 2 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment.
[5] At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST; Therasse et al. 2000). A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension and is ≥20 mm with conventional techniques or is ≥10 mm with spiral computed tomography (CT) scan (longest diameter to be recorded). Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements (see Protocol Attachment JMHO.5).
[6] Adequate organ function including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and
bands) count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L, and
hemoglobin ≥9 g/dL.
• Hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN), alkaline
phosphatase (AP), alanine transaminase (ALT) and aspartate transaminase
(AST) ≤3.0 x ULN (AP, AST, and ALT ≤5 x ULN is acceptable if liver
has tumor involvement).
• Renal: calculated creatinine clearance (CrCl) ≥45 mL/min based on the
standard Cockcroft and Gault formula (Cockcroft and Gault 1976). (See
Protocol Attachment JMHO.6)
[7] Estimated life expectancy of at least 12 weeks.
[8] For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding.
For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.
[9] Patient compliance and geographic proximity that allow adequate
follow up.
[10] Patient or his/her legal representative must sign an informed consent
document.
[11] Patients must be at least 18 years of age. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[12] 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.
[13] Have previously participated in a study involving pemetrexed.
[14] Have a mixed histological diagnosis of SCLC and NSCLC.
[15] Have a serious concomitant systemic disorder that, in the opinion of
the investigator, would compromise the patient’s ability to adhere to the protocol.
[16] Have an active infection (≥38.5ºC and/or receiving intravenous
antibiotic therapy).
[17] Have 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 (Protocol Attachment JMHO.8).
[18] Have had recent (within 30 days of study treatment) or concurrent yellow fever vaccination.
[19] Have had a prior malignancy other than SCLC, 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.
[20] Symptomatic central nervous system (CNS) metastases and asymptomatic CNS metastases requiring concurrent corticosteroid therapy. Treated stable CNS metastases are allowed; the patient must be stable after radiotherapy for ≥2 weeks and off of corticosteroids for ≥1 week.
[21] Presence of clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
[22] Significant weight loss (that is, ≥10%) over the 6 week period prior to study entry.
[23] Concurrent administration of any other antitumor therapy.
[24] Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose ≤1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
[25] Inability or unwillingness to take folic acid or vitamin B12 supplementation.
[26] Inability to take corticosteroids. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is to compare pemetrexed plus carboplatin with etoposide plus carboplatin in terms of overall survival (OS) of previously untreated patients with ED-SCLC |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| 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.8.5 | 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
|
details see protocol section 3.1:
Treatment consists of 6 cycles of therapy.
A patient receiving benefit from treatment may receive additional cycles (Section 5.5) until he/she meets the criteria for discontinuation (Section 4.3.1).
After approx. 1270 deaths, the database will be validated + “locked” for final analysis |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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