E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated patients with ED-SCLC |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
|
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 モsensitiveヤ 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 モsensitiveヤ 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 |
[1] Histological or cytological diagnosis of ED-SCLC, including
malignant pleural effusion.
[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).
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[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.
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[16] Have an active infection (>=38.5ᄎC 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 study JMHO is
overall survival; the experimental arm (pemetrexed/carboplatin) is expected to be
noninferior to the control arm (etoposide/carboplatin) |
|
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 | No |
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 | Information not present in EudraCT |
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 | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |