Clinical trial NCT01326767: Central European Society for Anticancer Research (CESAR) Study of Paclitaxel Therapeutic Drug Monitoring
Official title: An Open-Label, Randomized, Parallel Group Study of Patients Treated With Paclitaxel With Standard Dosing Versus Pharmacokinetic Guided Dose Adjustment in Patients With Advanced Non Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Central European Society for Anticancer Drug Research
Sponsor class: OTHER
Collaborators: name: Saladax Biomedical, Inc.
name: Cantonal Hospital of St. Gallen
name: University Hospital, Basel, Switzerland
name: Assign Data Management and Biostatistics GmbH
name: Wake Forest University
name: University Hospital, Essen
First posted: 2011-03-31
Enrollment: 366
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Grad 4 Neutropenia
timeFrame: up to 6 weeks on treatment
Secondary outcomes:
measure: Objective tumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1)
timeFrame: 24 months
measure: Progression free survival
timeFrame: 24 month
measure: Overall survival
timeFrame: 24 month
measure: Overall neutropenia
timeFrame: 24 month
measure: Hematological / non-hematological toxicites
timeFrame: 24 months
measure: Cumulative dose and dose intensity of paclitaxel and platinum drug
timeFrame: 24 months
measure: Incidence of changes from cisplatin to carboplatin and reasons thereof
timeFrame: 24 months
measure: Overall rate of febrile neutropenia and hospitalization due to chemotherapy-associated adverse events
timeFrame: 24 months
measure: Health economic analysis using QoL Questionnaires
timeFrame: 24 months
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: CESAR Study Center
city: Bonn
country: Germany
facility: CESAR study center
city: Essen
country: Germany
facility: CESAR Study Center
city: Gerlingen
country: Germany
facility: CESAR study center
city: Großhansdorf
country: Germany
facility: CESAR study center
city: Halle an der Saale
country: Germany
facility: CESAR Study Center
city: Leer
country: Germany
facility: CESAR Study Center
city: Löwenstein
country: Germany
facility: CESAR Study Center
city: Munich
country: Germany
facility: CESAR Study Center
city: Tübingen
country: Germany
facility: CESAR Study Center
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
Study officials:
affiliation: Central European Society for Anticancer Drug Research
name: Markus Joerger, MD PhD
role: STUDY_CHAIR
affiliation: Central European Society for Anticancer Drug Research
name: Ulrich Jaehde, PhD
role: STUDY_DIRECTOR
affiliation: Eberhard-Karls-Universität Tübingen
name: Frank Mayer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joerger M, von Pawel J, Kraff S, Fischer JR, Eberhardt W, Gauler TC, Mueller L, Reinmuth N, Reck M, Kimmich M, Mayer F, Kopp HG, Behringer DM, Ko YD, Hilger RA, Roessler M, Kloft C, Henrich A, Moritz B, Miller MC, Salamone SJ, Jaehde U. Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2016 Oct;27(10):1895-902. doi: 10.1093/annonc/mdw290. Epub 2016 Aug 8.