E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced non-squamous non small cell lung cancer |
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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 | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
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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 | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
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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 |
The primary objective of this study is to determine the correlation between TS expression and PFS. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows: - To determine the objective tumour response rate and overall survival rate at 18 months. - To determine the level of concordance between local versus central histology review. - To determine the biological characteristics of the more favourable (PFS ≥ 5.2 months) and less favourable (PFS <5.2 months) outcome groups. - To assess biomarkers relevant to the disease state and their correlation to clinical outcome.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The current Summary of Product Characteristics (SmPC) for pemetrexed will form the basis of patient selection. Patients are eligible to be included in the study only if they meet all of the following criteria: 1. Histological diagnosis of NSCLC which, in the opinion of the local pathologist and the treating physician, is non-squamous cell histology. Pathology must be reviewed and confirmed prior to enrollment at the investigational site where the patient is entered. Patients will be enrolled based on local diagnosis; however, an independent centralised pathology review will be performed on all enrolled patients. 2. Adequate tumour biopsy specimen must be available for TS assessment. The local diagnostic slides, pathology report and tissue material must be available for central review. 3. Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or Stage IV prior to induction therapy, as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer, that is not amenable to curative therapy. 4. Have ECOG performance status of 0-1. 5. Have had no prior systemic treatment (for example chemotherapy, vaccination etc) for lung cancer, including previous adjuvant and neoadjuvant therapy. 6. Previous palliative radiotherapy to non-target metastatic lesions is allowed to <25% of the bone marrow (Cristy & Eckerman, 1987). This should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study enrollment. Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumour progression has been documented in these lesions since the end of radiation therapy. 7. At least 1 unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST). The lesion should be at least 10mm in longest diameter by spiral computerized tomography (CT) scan, or at least 20mm by standard techniques. Tumour assessment at baseline should preferably be done with CT scan, although positron emission tomography (PET)-CT scans are acceptable for inclusion. (CT scans should be used throughout the study for all further treatment assessments). Ultrasound may not be used for tumour measurements. 8. Estimated life expectancy of at least 12 weeks. 9. Patient compliance and geographic proximity that allow adequate follow up. 10. Adequate organ function, including the following: a. Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) >=1.5 x 109/L, platelets >=100 x 109/L, and haemoglobin >=9 g/dL. b. Hepatic: bilirubin <=1.5 times the upper limit of normal (x ULN); alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) <=3.0 x ULN (AP, AST, and ALT <=5 x ULN is acceptable if liver has tumour involvement). c. Renal: calculated creatinine clearance (CrCl) >=45 mL/min based on the original weight based Cockcroft and Gault formula. 11. Males or females at least 18 years of age, and capable of giving informed consent. 12. 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 3 months after the treatment period; must have a negative serum or urine pregnancy test within 3 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.
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: 13. Have small cell, large cell neuroendocrine or carcinoid histology, squamous cell carcinoma or tumours with a predominantly squamous component. 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. Have a serious, uncontrolled medical condition that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. 16. Have a second primary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer that is considered cured by surgical resection or radiation). Patients who had another malignancy in the past, but have been disease-free for more than 5 years are eligible. 17. Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and the investigator is convinced that the patient can take part). A screening CT scan or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required. 18. Are receiving concurrent administration of any other systemic antitumour therapy, including adjuvant chemotherapy. 19. Have clinically detectable (by physical examination) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry. 20. Have received a recent (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination. 21. Are unable 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). 22. Are unable or unwilling to take folic acid, vitamin B12 supplementation, or corticosteroids. 23. Are pregnant or breastfeeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Progression-Free Survival (PFS) Time: Objective PFS time is defined as the time from the date of induction treatment to the first date of objectively determined PD or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last objective progression-free disease assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study drug) prior to objectively determined disease progression or death, PFS will be censored at the date of the last objective progression-free disease assessment prior to postdiscontinuation chemotherapy. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
The role of Thymidylate Synthase expression. |
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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) | 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 | No |
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) | No |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |