Carcinoma, Non-Small-Cell Lung
Conditions
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.
Interventions
DRUGPaclitaxel dosing according to SmPC
Paclitaxel i.V. Up to 6 cycles Dosing according to SmPC
DRUGIndividualized pharmacokinetically driven paclitaxel dosing
Paclitaxel i.V. Up to 6 cycles Dosing based on patient age, gender, severity of neutropenia and Paclitaxel plasma concentration
Sponsors
Saladax Biomedical, Inc.
Cantonal Hospital of St. Gallen
University Hospital, Basel, Switzerland
Assign Data Management and Biostatistics GmbH
Wake Forest University
University Hospital, Essen
Central European Society for Anticancer Drug Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Objective tumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1) | 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 | — |
| Cumulative dose and dose intensity of paclitaxel and platinum drug | 24 months | — |
Countries
Germany, Switzerland
Outcome results
None listed