Randomized Phase II Trial of Three-weekly Cisplatinum and Pemetrexed versus Split-dose d1 and d8 Cisplatinum and Pemetrexed In Advanced and Inoperable Non-squamous Non-small-cell lung cancer (NSCLC)
- Conditions
- Advanced and inoperable Non-sqamous Non-small-cell lung cancerMedDRA version: 18.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001963-37-DE
- Lead Sponsor
- niversitätsklinikum Essen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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 < 75 years
6. Adequate organ function, including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) = 1.5 x 10^9/L, platelets = 100 x 10^9/L, and hemoglobin = 9 g/dL
• Hepatic: bilirubin = 1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT) = 3.0 x ULN (AP, AST, and ALT = 5 x ULN is acceptable if the liver has tumour involvement)
• Renal: calculated creatinine clearance (CrCl) = 45 mL/minute based on the standard Cockcroft and Gault formula, and creatinine = 1.5 mg/dL
7. Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis 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.
8. Patient must understand and sign an informed consent document before the start of specific protocol procedures.
9. A pretreatment FFPE tumour biopsy must be available for central biomarker analysis. If consented by the patient and clinically feasible, a fresh pretreatment biopsy is obtained and submitted for central biomarker analysis.
10. Female patients with childbearing potential must use highly effective methods of contraception (combined oral contraceptives, hormon-releasing intrauterine contraceptive device, hormonal contraceptive implants, hormonal contraceptive injectables)
or have sexual intercourse with a vasectomised partner only
during and for 6 months after the study
and their pregnancy test must be negative within 7 days prior to study enrollment.
A female subject is considered to be of childbearing potential unless she is age = 50 years and naturally amenorrhoeic for = 2 year or unless she is surgically sterile.
Male patients must agree to use condoms during the study and for 6 months after the study if their partner is of childbearing potential and does not use highly effective method of contraception
11. Estimated life expectancy of = 12 weeks.
12. Patient compliance and geographic proximity that allow adequate follow up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method