NCT01326767

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
366

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Mar 2011

Typical duration for phase_3

Geographic Reach
2 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2011

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

March 29, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 31, 2011

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

January 27, 2016

Status Verified

January 1, 2016

Enrollment Period

3.8 years

First QC Date

March 29, 2011

Last Update Submit

January 26, 2016

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

  • Grad 4 Neutropenia

    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.

    up to 6 weeks on treatment

Secondary Outcomes (9)

  • 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

  • Hematological / non-hematological toxicites

    24 months

  • +4 more secondary outcomes

Study Arms (2)

Paclitaxel dosing according to SmPC

ACTIVE COMPARATOR
Drug: Paclitaxel dosing according to SmPC

Individualized pharmacokinetically driven paclitaxel dosing

EXPERIMENTAL

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

Interventions

Paclitaxel dosing according to SmPCDRUG

Paclitaxel i.V. Up to 6 cycles Dosing according to SmPC

Paclitaxel dosing according to SmPC
Individualized pharmacokinetically driven paclitaxel dosingDRUG

Paclitaxel i.V. Up to 6 cycles Dosing based on patient age, gender, severity of neutropenia and Paclitaxel plasma concentration

Individualized pharmacokinetically driven paclitaxel dosing

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

CESAR Study Center

Bochum, Germany

Location

CESAR study center

Bonn, Germany

Location

CESAR Study Center

Essen, Germany

Location

CESAR study center

Gerlingen, Germany

Location

CESAR study center

Großhansdorf, Germany

Location

CESAR Study Center

Halle, Germany

Location

CESAR Study Center

Leer, Germany

Location

CESAR Study Center

Löwenstein, Germany

Location

CESAR Study Center

Munich, Germany

Location

CESAR Study Center

Tübingen, Germany

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

  • 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.

    PMID: 27502710DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Markus Joerger, MD PhD

    Central European Society for Anticancer Drug Research

    STUDY CHAIR

  • Ulrich Jaehde, PhD

    Central European Society for Anticancer Drug Research

    STUDY DIRECTOR

  • Frank Mayer, MD

    Eberhard-Karls-Universität Tübingen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 29, 2011

First Posted

March 31, 2011

Study Start

March 1, 2011

Primary Completion

December 1, 2014

Study Completion

December 1, 2014

Last Updated

January 27, 2016

Record last verified: 2016-01

Locations

CH(1)DE(10)