E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced (Stage IIIB or IV) NSCLC previously treated with 4 cycles of a platinum-based chemotherapy (for Traceva®). |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
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 | 14.0 |
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 |
- Outcome Measure: Overall survival (OS): First-line maintenance Tarceva versus Tarceva at time of disease progression (Timeframe: 42 months) |
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E.2.2 | Secondary objectives of the trial |
- Outcome Measure: Progression-free survival (PFS): First-line maintenance Tarceva versus placebo (tumour assessments according to RECIST criteria) (Timeframe: 42 months)
- Outcome Measure: Overall response rate (ORR): First-line maintenance Tarceva versus placebo (Timeframe: 42 months)
- Outcome Measure: Disease control rate (DCR): First-line maintenance Tarceva versus placebo (Timeframe: 42 months)
- Outcome Measure: Safety: Incidence of adverse events (Timeframe: 42 months) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Roche Clinical Repository (RCR) project for Identifying the biomarkers that are predictive of response to erlotinib treatment (in terms of dose, safety and tolerability) and will help to better understand the pathogenesis, course and outcome of the cancer, NSCLC in particular and related diseases.
Protocol version A, see section 5.6. |
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E.3 | Principal inclusion criteria |
- Adult patients, >/= 18 years of age (or >/= legal age of consent if greater than 18)
- Advanced or recurrent (Stage IIIb) or metastatic (Stage IV) non-small cell lung cancer (NSCLC)
- Completion of 4 cycles of platinum-based chemotherapy without progression (end of last chemotherapy cycle </= 28 days prior to randomization)
- ECOG performance status 0-1
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E.4 | Principal exclusion criteria |
- Prior exposure to agents directed at HER axis (e.g. erlotinib, gefitinib, cetuximab)
- Patients whose tumours harbour an EGFR activating mutation
- Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease before screening (platinum-based chemotherapy)
- Use of premetrexed in maintenance setting (pemetrexed is allowed during the chemotherapy run-in)
- Patients who have undergone complete tumour resection after responding to the platinum-based chemotherapy during the screening phase
- Any other malignancies within 5 years, except for curatively resected carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ or organ confined prostate cancer
- CNS metastases or spinal cord compression that has not been definitely treated with surgery and/or radiation, or treated CNS metastases or spinal cord compression without stable disease for >/= 2 months
- HIV, hepatitis B or hepatitis C infection
- Any inflammatory changes of the surface of the eye
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is Overall Survival (OS) defined as the time from the date of randomization to the date of death, regardless of the cause of death. Patients who were alive at the time of the analysis will be censored at the date the patient was last known to be alive. Patients lost to follow-up in the survival follow-up will be considered as alive at the date of last contact. The analysis of survival will be performed after 632 events (deaths) have occurred. This is expected to occur approximately 14 months after last patient is randomized (see section 8.4 of the protocol). For patients still in the blinded phase, a visit with tumor assessment is required within the last 6 weeks before the clinical cut-off. For other patients still alive, a survival assessment is required within the last 6 weeks before the clinical cut-off. The analysis will be performed on the ITT population. The study will be declared positive if the primary analysis is statistically significant at its pre-specified significance levels (see section 8.3.3. of the protocol). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 460 events (death) have occurred |
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E.5.2 | Secondary end point(s) |
1 -PFS
2- ORR and DCR
3-safety and tolerability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 460 events (death) have occurred |
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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 | 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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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) | 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 | Yes |
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) | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 |
Brazil |
Canada |
Chile |
China |
Korea, Republic of |
Philippines |
Serbia |
South Africa |
Taiwan |
Thailand |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The study will end when the final analysis for the primary endpoint (Overall Survival)
has been performed. This will occur when the required numbers of events (460 deaths) is achieved, which is expected to happen approximately 10 months after the last patient has been randomized.
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |