| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-small Cell Lung Cancer |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
|
| 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 |
| Evaluate in parallel the efficacy of 2 different Tarceva-containing regimens as first-line therapy measured as the percentage of patients that have progressed at 6 months among stage IIIB/IV NSCLC patients selected on the basis of EGFR protein overexpression and/or increased EGFR gene copy numbers. |
|
| E.2.2 | Secondary objectives of the trial |
• Select the better of these 2 regimens for testing in future studies;
• Obtain estimates of PFS, overall survival, and tumor response for planning future studies;
• Explore potential correlations between clinical outcome and biomarkers of interest, including EGFR protein overexpression and/or increased EGFR gene copy numbers in this population;
• Evaluate in parallel the safety of these regimens in this population.
Optional Proteomic Analysis
For those who consent, serum from peripheral blood will be taken prior to the first dose of the drug and shipped to a central laboratory. MALDI-TOF mass spectrometry analysis will be performed to determin if specific proteins or protein patterns identify patients who are more likely or less likely to gain benefit
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
1) Histologically or cytologically (fine needle aspirate [FNA], sputum sample, or bronchial washing/lavage) documented advanced (stage IIIB or IV) NSCLC;
2) Age equal to or greater than 18 years;
3) ECOG PS 0, 1, or 2;
4) Predicted life expectancy equal to or greater than 12 weeks;
5) No prior therapy for advanced (stage IIIB or IV) NSCLC;
6) Prior to randomization, at least 1 of the 2 EGFR pathway markers must be positive
7) Radiologically measurable or evaluable disease as defined in Section 9.3.1.3;
8) Adequate hematopoietic, hepatic and renal function defined as follows:
- ANC equal to or greater than 1.5 x 10^9/L and platelet count equal to or greater than 100 x 10^9/L;
- Bilirubin less than or equal to 1.5 times the ULN, ALT (SGPT) less than or equal to 2.5 x ULN (or less than or equal to 5 x ULN in case of liver metastases);
- Serum creatinine less than or equal to 1.5 x ULN;
9) Accessible for repeat dosing and follow-up;
10) Patients with reproductive potential (eg, females menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures for the duration of study drug therapy and for at least 2 weeks after completion of study drug therapy. Female patients of child-bearing potential must provide a negative pregnancy test (serum or urine) less than or equal to 7 day prior to randomization;
11) Written informed consent to participate in the study according to the IRB.
|
|
| E.4 | Principal exclusion criteria |
Patients who meet any of the following exclusion criteria are not to be enrolled in this study:
1) Any prior or concurrent anticancer therapy (surgery, radiation, chemotherapy, or molecularly-targeted therapy) for advanced NSCLC, with the exception of surgical resection of an isolated brain metastasis and palliative radiation therapy. The patient must have fully recovered from surgery prior to the first dose of study drug. Palliative radiation therapy is allowed provided the treatment was not to the sole site of disease, concluded within 48 hours of first dose of study drug, and the patient was free of toxicity;
2) Any prior treatment with an EGFR inhibitor (eg, erlotinib, gefitinib, cetuximab, panitumumab, lapatinib), including neoadjuvant or adjuvant;
3) Other malignancies from which the patient has NOT been disease free for at least 5 years, except for adequately treated basal cell or squamous cell skin cancer;
4) Uncontrolled brain metastases (symptomatic brain metastases that are potentially life-threatening or require active treatment). If prior palliative treatment for brain metastases was administered, the patient should be neurologically stable and off steroids for a minimum of 2 weeks. A baseline CT scan of the brain is not required to rule out metastases unless there is clinical suspicion of central nervous system (CNS) involvement;
5) Gastrointestinal abnormalities, including inability to take oral medication, requirement for IV alimentation, active peptic ulcer or prior surgical procedures affecting absorption;
6) Ocular inflammatory or infectious conditions that have not be completely resolved prior to randomization;
7) Peripheral neuropathy less than or equal to grade 2;
8) Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction (within the 3 months prior to randomization) or serious cardiac arrhythmia requiring medication;
9) Active infection or serious underlying medical condition that would impair the ability of the patient to receive protocol treatment;
10) Women who are pregnant or breast-feeding and women or men not practicing effective birth control;
11) Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent;
12) Allergic reaction to compounds of similar chemical composition to the study drugs (Tarceva, paclitaxel, and carboplatin or their excipients).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy
Progression-free Survival
The primary endpoint will be the PFS rate at 6 months. PFS will be defined as the time from randomization until the first day radiological and/or symptomatic disease progression is documented or until death in the absence of progression. Patients who do not progress will be censored at the last day they were known to be free of progression by objective tumor measurements. Patients who receive other therapy prior to documented disease progression (eg, radiotherapy or other chemotherapy) will be censored the day this subsequent therapy started.
|
|
| 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 | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | 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
|
| Arm A, patients will receive daily Tarceva until disease progression is documented radiographically. Arm B, Tarceva will be intercalated with 4 cycles of chemotherapy, After the 4 cycles, administeration daily as a single agent until disease progression is documented radiographically, the patient has symptomatic progression, the patient experiences intolerable toxicity, the patient refuses additional therapy, until death, or for a max of 24 months. |
|
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
Print
