E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with locally advanced, unresectable/inoperable, Stage III, nonsquamous NSCLC without malignant pleural/pericardial effusion |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To compare the overall survival of patients with locally advanced, Stage III NSCLC of predominantly nonsquamous histology (hereafter simply referred to as nonsquamous) treated with pemetrexed plus cisplatin and concurrent TRT, followed by consolidation chemotherapy with pemetrexed (Arm A) versus etoposide plus cisplatin and concurrent TRT, followed by consolidation with cytotoxic chemotherapy of choice (Arm B). |
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E.2.2 | Secondary objectives of the trial |
• to compare progression-free survival (PFS) between the 2 arms
• to compare the first sites of disease failure in terms of relapse: within the radiation treatment field; at the edge of the radiation field; distant disease; or some combination of these
• to compare the objective response rate (complete response [CR] + partial response [PR]) between the 2 arms
• to compare 1-, 2-, and 3-year absolute survival rates between the 2 arms
• to assess patient-reported outcomes (PROs) between the 2 arms using the MD Anderson Symptom Inventory – Head and Neck (MDASI-HN) instrument , and a swallowing diary
• to estimate the incidence of adverse events from each treatment arm
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Present with histological proven or cytological diagnosis of NSCLC that is defined as nonsquamous (squamous cell histology and/or mixed small cell, non-small cell histology is not permitted)
[2] Unresectable Stage IIIA or IIIB NSCLC (without malignant pleural/pericardial effusion).
[3] Have an ECOG functional status score of 0 or 1
[4] Have tumor lesion measurable according to Response Evaluation Criteria in Solid Tumors
[5] Have adequate pulmonary function defined as in the protocol
[6] Have normal organ and marrow function as defined in the protocol
[7] Weight loss < or = 10% in the preceding 3 months
[8] Estimated life expectancy > 12 weeks
[9] Age > or = 18 years
[10] Signed informed consent from the patient
[[11] For women: must be surgically sterile, postmenopausal, 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
[12] Are compliant with study procedures and should live in a geographic proximity that facilitates adequate follow-up.
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E.4 | Principal exclusion criteria |
[13] Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
[14] Have myocardial infarction within the preceding 6 months or symptomatic congestive heart failure, unstable angina pectoris, or uncontrolled cardiac arrhythmia
[15] Have received treatment within the last 30 days with any other investigational agents that have not received regulatory approval for any indication at the time of study entry
[16] Have disease that is currently amenable to surgery
[17] Had prior thoracic or head/neck radiation. However, other prior radiotherapy is allowed. Patients must have recovered from the toxic effects of the treatment prior to study enrollment. Patients may not have received whole pelvis radiation or radiation to more than 25% of their bone marrow (Cristy and Eckermann 1987)
[18] Patients whose radiation treatment plans encompass a volume of whole lung receiving > or = 20 Gy in total (V20) of more than 35% of lung volume
[19] Concurrent cancer from another primary site requiring treatment of any kind within the past 5 years. Exemptions to this will be permitted on a case-by-case basis after prior approval by the lead Lilly physician or designate if the investigator believes the patient’s risk of recurrence and death is very low. Curatively treated nonmelanoma skin cancer or in situ carcinoma of any origin is allowed.
[20] Are pregnant, breast feeding, or unwilling to use adequate contraception
[21] Patients with immune deficiency (for example, HIV positive)
[22] Are unable to interrupt aspirin at a dose < or = 1.3 g/day or other nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed
[23] Are unable/unwilling to take folic acid, vitamin B12, and dexamethasone
[24] Have contraindication or rejection of the use of corticosteroids within 30 days of enrollment, or concurrent yellow fever vaccination (within 30 days of study enrollment)
[25] Presence of fluid accumulations in third spaces; for example, ascites or pleural effusion, which can be detected clinically (during physical examination), and which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study
[26] Have evidence of clinical hearing loss. Patients who have hearing loss based solely on conduction deficits demonstrated on audiogram may be entered into the study.
[27] Had prior systemic chemotherapy for lung cancer. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is overall survival (OS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at a time to include at least 355 deaths |
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E.5.2 | Secondary end point(s) |
Progression free survival, tumour response rate, patient reported outcomes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 | No |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
China |
France |
Germany |
Greece |
India |
Korea, Democratic People's Republic of |
Netherlands |
Portugal |
Spain |
Taiwan |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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last visit of last patient |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |