Study to evaluate the efficiency of first-line-treatment including chemotherapy plus Bevacizumab according to Thymidylate Synthetase-Production in patients with inoperable non-small Cell Lung Cancer – Stage IV
- Conditions
- on-squamous advanced Non-Small-Cell Lung-Cancer (Stage IV)MedDRA version: 16.0Level: LLTClassification code 10025077Term: Lung carcinoma stage IVSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-002145-35-DE
- Lead Sponsor
- Aktion Bronchialkarzinom (ABC) e.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 146
1. Histological confirmed Non-Small-Cell lung cancer
2. Tumor stage IV (UICC 7th Version)
3. The following histological tumor types are eligible:
- Adenocarcinoma (including adenocarcinomas with bronchioloalveolar differentiation)
- Large Cell carcinoma without neuroendocrine differentiation
- Mixed Cell Carcinoma without small cell fraction and without predominant squamous cell fraction
- undifferentiated non-small-cell-carcinoma
4. No previous chemotherapy for stage IV NSCLC
5. Adjuvant or neoadjuvant chemotherapy for NSCLC must be
completed at least one year prior to study enrolment (from end of chemotherapy)
6. No previous treatment with Pemetrexed or Bevacizumab
7. Patients with prior radiation therapy may be eligible for this study if they meet the following guidelines:
- Previous radiation therapy is allowed to <25% of the bone marrow (Cristy and Eckerman 1987), but 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 thoracic radiotherapy must be completed 30 days before study enrollment
- Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been
documented in these lesions since the end of radiation therapy
- Palliative extrathoracic radiotherapy to preexisting lesions may continue on study; however, these lesions may not be included as sites of measurable disease.
8. At least 4 weeks since last major surgery
9. Age = 18 and = 70 years
10. ECOG = 1
11. Adequate hematological laboratory parameters:
- Hemoglobin = 9 g/dl
- Neutrophils = 1.500 µl
- WBC = 3.000 µl
- Platelets = 100.000 µl
12. Adequate hepatic laboratory parameters:
- Total Bilirubin = 1,5 x ULN
- Alkaline phosphatase = 3 x ULN
- AST(GOT) < 2,5 ULN in patients without liver metastasis < 5 x ULN in patients with liver metastasis ULN = (upper limit of normal)
- ALT(GPT) < 2,5 ULN in patients without liver metastasis < 5 x ULN in patients with liver metastasis ULN = (upper limit of normal)
13. Adequate renal laboratory parameters:
- Creatinine Clearance > 50 ml/min
- Urine dipstick for proteinuria < 2+
Patientients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1 g of protein in 24 hours
14. Normal cardiac function defined by New York Heart Association – NYHA Class I and Class II
15. Electrocardiogram without significant signs of cardiac arrhythmias
16. Provision of informed consent according to local regulatory requirements prior to any protocol specific treatment
18. Measurable lesion according to RECIST 1.1
19. Negative pregnancy test for women of childbearing potential unless they are postmenopausal at baseline.(Postmenopausal women must have been amenorrheic at least for 12 months to be considered of non childbearing potential)
20. Women of child bearing potential and men to be willing to use an acceptable method to avoid pregnancy at least one month before study start. Examples: oral contraceptives (sole application of oral contraceptives is not sufficient), diaphragm pessary, intrauterine device (spiral), condom plus diaphragm pessary plus spermicide
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 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for
1. Histological confirmed predominant squamous cell carcinoma
2. Presence of activating EGFR mutations in exons 18-21
3. Pregnancy or lactation period
4. Have known central nervous system disease, other than stable, treated brain metastasis. Stable, treated brain metastasis is defined as metastasis having no evidence of progression or
hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and posttreatment brain imaging. Patients should be off corticosteroids for 1 week at the time of the post-treatment brain CT/MRI. Anticonvulsants are allowed. Treatment for brain metastases may
include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician, and must have been completed > 28 days prior to Day 1 of Cycle 1. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 8 weeks prior to Day 1 of Cycle 1 will be excluded
5. Evidence of tumor invading or abutting major blood vessels
6. Presence of a tracheobronchial fistula
7. History of abdominal fistula or fistulisation of urogenital tract,
gastrointestinal perforation or intra-abdominal abscess, inflammatory bowel disease, or diverticulitis within 6 months prior to study start
8. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of a CIS of the cervix, nonmelanomatous skin cancer, stable chronic lymphatic leukaemia,
non-muscle invasive bladder cancer or surgically treated or irradiated prostate cancer with no signs of recurrence for one year. Patients with other malignancies curatively treated and free of disease for at least 5 years will be discussed with the Principal Investigator before inclusion
9. Treatment with an investigational new drug, currently or within the last 28 days, and/or participation in another clinical trial, currently or during the last 12 weeks, and/or previous participation in this study.
10. History or presence of a mental disease or condition such as to interfere with the patient's ability to understand the requirements of the study and the intake of study medication according to study protocol.
11. Patients with any clinically significant disease that in the opinion of the investigator is likely to put the patient at risk or to interfere with the evaluation of the patient's safety and of the study outcome. This includes, but is not limited to:
- Immediate need for therapeutic intervention
- Clinically significant cardiac disease or myocardial infarction within the last 6 months
12. Have a history of hypertension, unless hypertension is well controlled upon study entry and the patient is on a stable regimen of antihypertensive therapy. Patients should not have any prior history of hypertensive crisis or hypertensive encephalopathy.
13. Non healing wound, ulcer or bone fracture
14. Fresh thrombosis under full dose therapy with anticoagulants
15. History of thrombotic disorders within the last 6 months prior to entry
16. Current or recent full-dose oral or parenteral anticoagulants, or thrombolytic agents for therapeutic purposes
17. Prophylactic use of anticoagulants is allowed; international normalized ratio should be <1.5 at study enrollment.
18. Current or recent use of ASS – Dosage > 325 mg/day
19. Current or recent use of Plavix/Clopidogrel, at doses >75 mg/d, dipyramidole, ticlopidine, cilostazol
20. Hemorrhagic diathesis, Hemophilia A, Hemophilia B
21. Implantation o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the activity of a first-line treatment related to Thymidylate Synthetase (TS) Expression in patients with non-squamous advanced Non-Small Cell Lung Cancer. The main efficacy parameter is the progression free survival (PFS).;Secondary Objective: - Overall survival<br>- Quality of life<br>- Response rate<br>- Explorative subgroup analyses (for example: LDH-level, gender, age, performance status, histology, smoking history)<br>- Molecular investigations<br>- Analysis of prognostic and predictive value of TS-Expression;Primary end point(s): Progression free survival (PFS).;Timepoint(s) of evaluation of this end point: PFS will be calculated from the date of start of treatment (cycle 1, day 1) to the date of first progression, death or date of last contact.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Quality of life<br>- Response rate<br>- Explorative subgroup analyses<br>- Molecular investigations;Timepoint(s) of evaluation of this end point: - Screening, day 1, day 84 and end of treatment (quality of life questionnaire)<br>- Total study duration