An exploratory, prospective phase II study to investigate progression-free survival, response and overall survival seen with pemetrexed/cisplatin and the role of thymidylate synthase expression.

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2008-006709-18-IE
• Date of registration: 10/03/2009
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Limited
• Public title: An exploratory, prospective phase II study to investigate progression-free survival, response and overall survival seen with pemetrexed/cisplatin and the role of thymidylate synthase expression.
• Scientific title: An exploratory, prospective phase II study to investigate progression-free survival, response and overall survival seen with pemetrexed/cisplatin and the role of thymidylate synthase expression.
• Date of first enrolment: 15/05/2009
• Target sample size: 68
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006709-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Ireland, United Kingdom

Key inclusion & exclusion criteria

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 pregnan
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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced non-squamous non small cell lung cancer
MedDRA version: 9.1 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB
MedDRA version: 9.1 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV

Intervention(s)

Trade Name: Alimta
Pharmaceutical Form: Powder for concentrate for solution for infusion

Primary Outcome(s)

Main Objective: The primary objective of this study is to determine the correlation between TS expression and PFS.

Secondary Objective: 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.

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.

Secondary ID(s)

H3E-BP-JMIK