Central European Society for Anticancer Research (CESAR) Study of Paclitaxel Therapeutic Drug Monitoring (CEPAC-TDM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Central European Society for Anticancer Drug Research
Sponsor:
Collaborators:
Saladax Biomedical, Inc.
Cantonal Hospital of St. Gallen
University Hospital, Basel, Switzerland
Assign Data Management and Biostatistics GmbH
Wake Forest School of Medicine
University Hospital, Essen
Information provided by (Responsible Party):
Central European Society for Anticancer Drug Research
ClinicalTrials.gov Identifier:
NCT01326767
First received: March 29, 2011
Last updated: November 16, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Paclitaxel dosing according to SmPC
Drug: Individualized pharmacokinetically driven paclitaxel dosing
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Central European Society for Anticancer Drug Research:

Primary Outcome Measures:
  • Grad 4 Neutropenia [ Time Frame: up to 6 weeks on treatment ] [ Designated as safety issue: Yes ]
    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:
  • Objective tumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: 24 month ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 24 month ] [ Designated as safety issue: No ]
  • Overall neutropenia [ Time Frame: 24 month ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Incidence of changes from cisplatin to carboplatin and reasons thereof [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Overall rate of febrile neutropenia and hospitalization due to chemotherapy-associated adverse events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Health economic analysis using QoL Questionnaires [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: March 2011
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Paclitaxel dosing according to SmPC Drug: Paclitaxel dosing according to SmPC
Paclitaxel i.V. Up to 6 cycles Dosing according to SmPC
Experimental: 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.
Drug: Individualized pharmacokinetically driven paclitaxel dosing
Paclitaxel i.V. Up to 6 cycles Dosing based on patient age, gender, severity of neutropenia and Paclitaxel plasma concentration

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326767

Contacts
Contact: Berta Moritz, PhD 00431522309312 berta.moritz@cesar.or.at
Contact: Max Roessler, PhD 00431522309316 max.roessler@cesar.or.at

Locations
Germany
CESAR Study Center Recruiting
Bochum, Germany
CESAR study center Recruiting
Bonn, Germany
CESAR Study Center Recruiting
Essen, Germany
CESAR study center Recruiting
Gerlingen, Germany
CESAR study center Recruiting
Großhansdorf, Germany
CESAR Study Center Not yet recruiting
Halle an der Saale, Germany
CESAR Study Center Recruiting
Leer, Germany
CESAR Study Center Recruiting
Löwenstein, Germany
CESAR Study Center Recruiting
Munich, Germany
CESAR Study Center Recruiting
Tübingen, Germany
Switzerland
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Markus Jörger, MD PhD    +41-71 494 1111    markus.joerger@kssg.ch   
Principal Investigator: Markus Jörger, MD, PhD         
Sponsors and Collaborators
Central European Society for Anticancer Drug Research
Saladax Biomedical, Inc.
Cantonal Hospital of St. Gallen
University Hospital, Basel, Switzerland
Assign Data Management and Biostatistics GmbH
Wake Forest School of Medicine
University Hospital, Essen
Investigators
Study Chair: Markus Joerger, MD PhD Central European Society for Anticancer Drug Research
Study Director: Ulrich Jaehde, PhD Central European Society for Anticancer Drug Research
Principal Investigator: Frank Mayer, MD Eberhard-Karls-Universität Tübingen
  More Information

Additional Information:
No publications provided

Responsible Party: Central European Society for Anticancer Drug Research
ClinicalTrials.gov Identifier: NCT01326767     History of Changes
Other Study ID Numbers: C-III-002, 2010-023688-16
Study First Received: March 29, 2011
Last Updated: November 16, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 30, 2014