Central European Society for Anticancer Research (CESAR) Study of Paclitaxel Therapeutic Drug Monitoring
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Drug: Individualized pharmacokinetically driven paclitaxel dosing
- Registration Number
- NCT01326767
- Lead Sponsor
- Central European Society for Anticancer Drug Research
- Brief Summary
This study will be performed on grade IIIb and grade IV Non Small Cell Lung Cancer (NSCLC) chemotherapy naive patients with good performance status. In course of this study, patients will be treated with Paclitaxel in combination with either Cisplatin or Carboplatin in a maximum of six therapy cycles. The goal of this study is to determine, if a pharmakokinetic driven dose adaptation of paclitaxel leads to a reduction of of grade 4 neutropenia, compared to conventional Paclitaxel dosing, without affecting progression free survival and overall survival.
This study includes a biomarker analysis and an optional genetic substudy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 366
- Capable of understanding the protocol requirements and risks, and providing written informed consent.
- Patients with histologically confirmed NSCLC (stage IIIB-IV).
- Patients considered for first-line palliative chemotherapy with paclitaxel in combination with either cisplatin or carboplatin. Patients having received prior adjuvant non taxane-containing adjuvant chemotherapy are eligible.
- At least one bidimensionally measurable lesion according to RECIST 1.1.
- ECOG Performance Status (ECOG-PS) status ≤ 2.
- Female or male patients of 18 to 75 years of age at randomization
- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods (condom).
- An absolute neutrophil count >1,500 cells/ mm3 (= 1.5 G/l).
- Platelet count > 100,000/mm3.
- Total bilirubin ≤ 2 x upper limit of normal.
- AST and ALT ≤ 2.5 x upper limit of normal, or ≤ 5 x upper limit of normal in case of liver metastases.
- Creatinine clearance (according to the Cockcroft-Gault formula) ≥30ml/min. For patients planned to receive Cisplatin: Creatinine clearance ≥60ml/min.
- Patients suffering from asymptomatic brain metastases can be enrolled in case corticosteroid therapy is not indicated. Prior irradiation must be completed at least 4 weeks prior to first cycle of treatment.
- Serious concomitant systemic disorders (e.g., active infection, severe heart disease, uncontrolled hypertension or diabetes mellitus) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
- A history of hypersensitivity reactions to drugs formulated in polyoxyethylated castor oil.
- Having received prior treatment with paclitaxel or cisplatin or carboplatin (other drugs/drug combinations are allowed).
- Concomitant treatment with any targeted drug (licensed or experimental) like bevacizumab or cetuximab.
- Any condition / concomitant disease not allowing chemotherapy with paclitaxel, the platinum compound (carboplatin or cisplatin) or required premedication for the treatment regimen.
- Pregnant/nursing women.
- Individuals known to be seropositive for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen or syphilis.
- Treatment with cytotoxic or biologic agents or any experimental drug within the 4 weeks prior to beginning treatment on this study.
- Secondary malignancy within the last five years, with the exception of adequately treated carcinoma-in-situ of the uterine cervix, basal-cell carcinoma of the skin and pTa or pTis urothelial cancer.
- Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
- Preexisting neuropathy > grade I NCI-CTC.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Paclitaxel dosing according to SmPC Paclitaxel dosing according to SmPC - Individualized pharmacokinetically driven paclitaxel dosing Individualized pharmacokinetically driven paclitaxel dosing In the first treatment cycle, the Paclitaxel dose is adapted depending on the age and the gender of the patient. In the treatment cycles 2-6 the Paclitaxel dose is adapted based on individual PK data and toxicities.
- Primary Outcome Measures
Name Time Method Grad 4 Neutropenia up to 6 weeks on treatment The rate of grade 4 Neutropenia during the second treatment cycle between the conventional Paclitaxel dosing arm and pharmacokinetically driven Paclitaxel dosing arm is compared. At the same time progression free survival and overall survival must not be affected.
- Secondary Outcome Measures
Name Time Method Objective tumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1) 24 months Progression free survival 24 month Overall survival 24 month Overall neutropenia 24 month Overall neutropenia ( i.e. during total chemotherapy duration) assessed from clinical hematology data and by model-based estimations of individual neutrophil curves
Hematological / non-hematological toxicites 24 months Hematological (leucocytopenia, anemia, thrombocytopenia) and non-hematological toxicities (e.g. neurological, musculosceletal and gastrointestinal adverse events)
Cumulative dose and dose intensity of paclitaxel and platinum drug 24 months Incidence of changes from cisplatin to carboplatin and reasons thereof 24 months Overall rate of febrile neutropenia and hospitalization due to chemotherapy-associated adverse events 24 months Health economic analysis using QoL Questionnaires 24 months
Trial Locations
- Locations (3)
CESAR Study Center
🇩🇪Tübingen, Germany
CESAR study center
🇩🇪Großhansdorf, Germany
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
CESAR Study Center🇩🇪Tübingen, Germany