Advanced and inoperable Non-sqamous Non-small-cell lung cancer MedDRA version: 18.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: ALIMTA
Product Name: ALIMTA
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: PEMETREXED
CAS Number: 137281-23-3
Concentration unit: mg milligram(s
Sponsors
Universitätsklinikum Essen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed diagnosis of non-squamous-cell non-small cell lung cancer (NSCLC) Stage IV 2. No prior systemic chemotherapy for lung cancer 3. At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST; version 1.1, Eisenhauer et al. 2009), longest diameter =10 mm with computed tomography (CT) scan [CT scan slice thickness no greater than 5 mm] , or = 20 mm with chest x-ray. Positron emission tomography (PET) scans and ultrasounds should not be used 4. ECOG performance status of 0 or 1 5. = 18 years of age =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Active participation in other clinical studies or treatment with any experimental drug within 30 days prior to study enrollment or during study participation 2. Patients with known somatic activating mutations of EGFR, as these patients should be offered EGFR-TKI treatment as first-line therapy. Detection of EGFR mutations and additional somatic mutations with relation to treatment will be performed centrally at the Universitätsklinikum Essen. In case immediate treatment initiation is required for medical reasons (such as superior vena cava syndrome, severely symptomatic disease) patients may be enrolled before results from EGFR testing are available. As EGFR-TKI treatment is equally effective in second-line therapy, such patients may remain on study treatment if a clinical benefit is derived. 3. Peripheral neuropathy of = CTCAE Grade 1 4. Inability to comply with protocol or study procedures 5. A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient’s ability to complete the study. 6. A serious cardiac condition, such as myocardial infarction within 6 months prior to study enrollment, symptomatic coronary artery disease, cardiac arrhythmia, or other heart disease, as defined by the New York Heart Association Class III or IV (functional capacity) 7. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment 8. Documented brain metastases unless the patient has completed successful local therapy for central nervous system metastases and has been off of corticosteroids for at least 4 weeks before enrollment. Brain imaging is required in symptomatic patients to rule out brain metastases,but is not required in asymptomatic patients. 9. The effect of third space fluid, such as pleural effusion and ascites, on pemetrexed is unknown. In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to pemetrexed administration. 10. Significant weight loss (that is, = 10%) over the previous 6 weeks before study entry 11. Significant hearing function impairment, especially high-frequency hearing function impairment 12. Any active or uncontrolled infection 13. Concurrent administration of any other antitumour therapy 14. Inability 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) 15. Inability or unwillingness to take folic acid or vitamin B12 supplementation 16. Inability to take corticosteroids 17. Hypersensitivity to cisplatinum or to any other platinum compound 18. Hypersensitivity to pemetrexed or to any of the excipients of ALIMTA® 19. Pregnant or breast-feeding patient 20. Yellow fever vaccination within the 30 days previous to study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate and compare objective response rates in both arms while defining toxicity profiles of both application schedules. Additionally, evaluation of biologically validated, potentially predictive biomarkers and identification of new biomarkers for therapy response, therapy resistance, and course of disease in formalin-fixed paraffin-embedded (FFPE) and fresh tumour specimens as well as circulating tumour cells (CTCs), obtained before treatment and, if applicable, during and after study treatment.;Secondary Objective: • Overall survival • Time to progression (TTP) • Treatment compliance • Treatment toxicity • Duration of treatment administration in both arms • Life quality analysis (by means of EORTC QLQ-C30 version 3.0) • Received dose-intensity cisplatinum (RDI) • Received dose intensity (RDI) pemetrexed • Cumulative dose cisplatinum • Documentation of outpatient or inpatient administration of treatment • Evaluation of predictive biomarkers for response or resistance to pemetrexed/cisplatin-based chemotherapy in NSCLC, in tumour specimens and in circulating tumour cells (CTCs) ;Primary end point(s): • Objective response rate in both treatment arms Response will be assessed in all patients who achieve six cycles of chemotherapy or less in case of prior tumour progression or trial termination due to toxicity. Treatment response will be analyzed according to RECIST 1.1 with standard computed tomography (CT) scans, chest x-ray, or chest MRI as done routinely also outside of clinical trials situations for survey of chemotherapy in patients with NSCLC. ;Timepoint(s) of evaluation of this end point: tumour assessment every second cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival • Time to progression (TTP) • Treatment compliance • Treatment toxicity • Duration of treatment administration in both arms • Life quality analysis (by means of EORTC QLQ-C30 version 3.0) • Received dose-intensity cisplatinum (RDI) • Received dose intensity (RDI) pemetrexed • Cumulative dose cisplatinum • Documentation of outpatient or inpatient administration of treatment • Evaluation of predictive biomarkers for response or resistance to pemetrexed/cisplatin-based chemotherapy in NSCLC, in tumour specimens and in circulating tumour cells (CTCs) ;Timepoint(s) of evaluation of this end point: • During treatment cycles: - D1 and end of study visit: Life quality analysis - D1, D8 and D15 and end of study visit: overall survival, treatment compliance, treatment toxicity, duration of treatment administration in both arms, received dose intensity cisplatinum and pemetrexed, cumulative dose cisplatinum, documentation of outpatient or inpatient administration of treatment - every second cycle and end of study visit: time to progression • During Follow Up (every 6 to 8 weeks): overall survival, time to progression, treatment toxicity (until 30 days after last application of study medication, relevant late toxicities) • Evaluation of predictive biomarkers: tumour specimens at baseline and optional in case of progression, CTCs on D1 and D8 cycle 1 and D1 cycle 2 | — |
Countries
Germany
Outcome results
None listed