| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients who have histologically or cytologically documented diagnosis of nonsquamous NSCLC (Stage IIIA, IIIB or IV at entry), with progressive disease after treatment with 1 prior chemotherapy regimen for locally advanced or metastatic disease, who are considered for second line therapy and who meet the other disease criteria. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029514 |
| E.1.2 | Term | Non-small cell lung cancer NOS |
|
| 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 progression free survival between Pemetrexed 500 mg/m² every 3 weeks + Erlotinib 150 mg daily and Pemetrexed 500 mg/m² every 3 weeks when given as second line therapy for the treatment of locally advanced or metastatic nonsquamous Non Small Cell Lung Cancer |
|
| E.2.2 | Secondary objectives of the trial |
Assess and compare the following variables in both treatment arms:
•safety and adverse events profile
•response rates
•disease control rates (percentage of randomized patients with best response of Stable Disease, Partial Response or Complete Response)
•time to treatment failure
•overall survival including 1-year survival rates
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Histological or cytological diagnosis of NSCLC with locally advanced or metastatic disease (Stage IIIA, IIIB or IV at entry) that is of nonsquamous histology and not amenable to curative therapy. Predominantly squamous cell, and/or mixed small cell, or non-small cell histology is not permitted.
[2] Non-smoker and smoker patients
[3] At least one unidimensionally measurable lesion meeting RECIST criteria. Positron emission tomography (PET scans) and ultrasound are not allowed.
[4] Patients must have failed one prior platinum-based chemotherapy regimen for advanced or metastatic disease (Stage IIIA, IIIB, or IV) and must be considered eligible for further chemotherapy following progression of their disease. Prior chemotherapy given as neoadjuvant or adjuvant therapy for early stage disease, completed at least 12 months prior to the diagnosis of advanced stage disease, will not be counted as a prior regimen. If neoadjuvant or adjuvant therapy for early stage disease has been completed earlier than 12 months prior to the diagnosis of advanced stage disease, patients cannot be enrolled. Chemotherapy must be completed at least 2 weeks prior to study enrollment and the patient must have recovered from the acute toxic effects of the regimen. Previous treatment with therapies not specifically directed to the HER axis (such as sorafenib and bevacizumab) is allowed, provided the targeted therapy was initiated concurrently with chemotherapy as part of first-line treatment, has been discontinued for at least 2 weeks prior to enrollment, and the patient has been recovered from acute toxic effects of therapy.
[5] Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis or chest for the treatment of NSCLC is not allowed.
Prior radiotherapy must be completed at least 4 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in this lesion since the end of radiation therapy.
[6] At least 4 weeks since any prior surgery. Patients who, in the opinion of the investigator, have fully recovered from surgery in less than 4 weeks may also be considered for the study.
[7] Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) Scale
[8] Estimated life expectancy of at least 8 weeks.
[9] Patient compliance and geographic proximity that allow adequate follow-up.
[10] Adequate organ function including the following:
• Adequate bone marrow reserve: Absolute neutrophils (segmented and bands) count (ANC) > or =1.5 x 109/L, platelets > or =100 x 109/L, and hemoglobin > or = 9 g/dL
• Hepatic: Bilirubin < or = 1.5 x ULN, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) < or = 3 x ULN (AP, AST and ALT <or = 5 x ULN is acceptable if liver has tumor involvement)
• Renal: Calculated creatinine clearance (CrCl) > or = 45 mL/min based on the standard Cockcroft and Gault formula and serum creatinine <1.5 x ULN
[11] Signed informed consent from patient.
[12] Males or females at least 18 years of age.
[13] 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.
|
|
| E.4 | Principal exclusion criteria |
[14] 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.
[15] Prior exposure to agents directed at the HER axis (e.g., Gefitinib, Erlotinib, Cetuximab, or Trastuzumab).
[16] Prior exposure to agents directed at Pemetrexed molecular targets (i.e., TS or DHFR inhibitors).
[17] Any known significant ophthalmologic abnormalities of the surface of the eye (The use of contact lenses is not recommended).
[18] Erlotinib and Pemetrexed are contraindicated in patients who have a history of severe hypersensitivity reaction to Erlotinib or Pemetrexed or to any other ingredient used in the formulation.
[19] Recent (within 30 days of enrolment) or concurrent yellow fever vaccination
[20] Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
[21] Patients under therapy with warfarin or coumarin derivatives.
[22] Pregnancy / Breast-feeding.
[23] Have a serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol.
[24] Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
[25] Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin doses < or =1.3 grams per day, for a 5-day period (8-day period for long-acting agents such as piroxicam).
[26] Central nervous system (CNS) metastases. Patients with CNS metastases will be excluded from entering the study, unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy. A screening CT or MRI before enrollment in the absence of a clinical suspicion of brain metastases is not required.
[27] Presence of clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
[28] 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.
[29] Concurrent administration of any other antitumor therapy.
[30] Inability or unwillingness to take folic acid or vitamin B12 supplementation.
[31] Inability to take corticosteroids.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival |
|
| 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 | 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) | 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 | 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.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| 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 | 8 |
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