Explore the Individual Treatment of Docetaxel and Paclitaxel in NSCLC, NPC and BRC by PK-guided Dosing Strategy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01891123
Recruitment Status : Unknown
Verified December 2015 by Li Zhang, Sun Yat-sen University.
Recruitment status was:  Recruiting
First Posted : July 2, 2013
Last Update Posted : December 9, 2015
Information provided by (Responsible Party):
Li Zhang, Sun Yat-sen University

Brief Summary:
As cytotoxic agents, DTX and PTX have a narrow therapeutic window. BSA dosing leads to great inter-individual PK variability, which is a major contributor for severe toxicity, especially in East-Asian populations. DTX exposures measured by area under plasma concentration-time curve (AUC), PTX exposures measured by the time above a plasma concentration of 0.05 µmol/L (TC>0.05), are the most biologic effects associated PK parameters for DTX and PTX, respectively, which could positively predict related toxicities such as neutropenia, peripheral neuropathy, etc. So, we conducted a randomized clinical trial to compare the effect on related toxicities and efficacy of PK-guided dosing strategy and BSA dosing strategy.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Breast Cancer Nasal Cancer Device: PK guided arm Drug: PTX 175mg/m2, DOC 75mg/m2 Not Applicable

Detailed Description:
3 populations were included: advanced NSCLC patients receive a single-agent docetaxel regimen palliative chemotherapy without restriction of lines; NPC patients receive paclitaxel and carboplatin doublet regimen whether as induction chemotherapy for local advanced patients or palliative chemotherapy for metastatic patients; BRC patients receive a single-agent docetaxel regimen after 4 cycles of adriamycin and cyclophosphamide for adjuvant chemotherapy. Patients are randomly assigned into the BSA-based dosing group and pharmacokinetically-guided dosing group. In the BSA-based dosing group, NPC patients receive paclitaxel (175mg/m2) and carboplatin (AUC=5) treatment, NSCLC and BRC patients receive docetaxel (75mg/m2) treatment, 3-weekly and for up to 6 cycles. BSA group and PK-guided group are with a same starting dose. DTX exposure (AUC) and PTX exposure (TC>0.05) are calculated from a published PK model with an established limited sampling strategy. Dose of subsequent cycles of PK-guided group patients is calculated base on the previous cycle PK results, according to optimal target algorithm. The optimal target for DTX exposure is 2.5 - 3.7 µg•h/mL. Dose reductions were permitted in both arms according to instructions. The study had a power of 80% to detect a 23% reduction of grade >3 neutropenia with PK-guided arm for DTX sub-study in NSCLC. A sample size of 100 NSCLC patients was estimated by using Fisher's exact test to provide a 5% two-sided alpha significance level to observe a decrease in the hematological toxicity with a power of 0.8. This is based on the reported toxicity rates of 85% with dose of 75mg/m2 and 63% with 60mg/m2. Objective response rate is evaluated by imaging examination (CT or MR scan) every 2 cycles. Toxicities are evaluated by patients' diary for toxicity reports and physician's evaluation at day 10 and day 21 at every cycle. Blood samples are collected every cycle. And survival information is collected by clinic and telephone follow-up. Research Hypothesis: 1. The concentrations variability dosed by BSA, and the limitation of BSA- and MTD-based dosing. 2. Verify that paclitaxel TC>0.05 and docetaxel AUC are the most relevant predictor of related toxicities and clinical outcomes. 3. Verify the feasibility of dosing algorithm based on paclitaxel TC>0.05 and docetaxel AUC, quantify its effect on both reducing toxicity and improving Effectiveness. 4. The effect of using dose modification and administration of G-CSF based on toxicity determined by paclitaxel TC>0.05 and docetaxel AUC measurement. 5. Prove the ability of PK-guided dosing strategy in reducing DTX and PTX related hematologic and non-hematologic toxicities, and the effect on treatment efficacy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Randomized Clinical Trial to Compare the Toxicities and Efficacy of Pharmacokinetically-guided and BSA Fixed Dosing Strategy of Docetaxel and Paclitaxel in Chinese Non-small Cell Lung Cancer, Nasopharyngeal Carcinoma, and Breast Cancer Patients.
Study Start Date : June 2013
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Placebo Comparator: body surface area
patients receive fixed dose of PTX or DOC based on body surface area every cycle, PTX 175mg/m2, DOC 75mg/m2. Patients should finish up to 6 cycles chemotherapy
Drug: PTX 175mg/m2, DOC 75mg/m2
patients receive PTX or DOC dose based on body surface area every cycle, PTX 175mg/m2, DOC 75mg/m2

Active Comparator: Detection Kit
PTX 175mg/m2, DOC 75mg/m2 at first cycle. the dose of PTX or DOC will adjust based on the pharmacokinetic results of previous cycle. A optimal target of PTX(TC>0.05) and DOC(AUC) have been set from published PK model with an established limited sampling strategy
Device: PK guided arm
the dose of PTX or DOC will adjust based on the plasma drug concentration of previous cycle
Other Name: pharmacokinetic guided dosing stratety

Primary Outcome Measures :
  1. Toxicities rate [ Time Frame: 3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks ]
    assess the toxicities rate and severity according to CTCAE v4.03, record the toxicities incident and grades from the first cycle to last cycle until the toxicities relieve or stabilize.

Secondary Outcome Measures :
  1. Object response rate [ Time Frame: up to 18 weeks ]
    assess the ORR according to RECIST v1.1, An imaging examination should be performed in 4weeks before treatment initiation, and patients are going to receive (CT or MR scan) every 2 cycles during the treatment, the methods should be identical with baseline.

  2. Survival Effectiveness [ Time Frame: 36 months ]
    after treatment discontinuation, PFS is recorded by imaging examination every 2 cycles (8 weeks) until tumor progression, other anti-cancer treatment start, trial ends or death. OS is recorded by clinic follow-up or telephone follow-up until death.

Other Outcome Measures:
  1. the quality of life of patients [ Time Frame: 3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed by pathology for advanced non small cell lung cancer, suitable for paclitaxel or docetaxel chemotherapy (clinical stage IV according to 2009 IASLC staging or recurrent NSCLC; receiving palliative chemotherapy independent of lines)
  • ECOG PS score: 0 to 2 points
  • Survival is expected to more than 3 month
  • Bone marrow reserve function is good, the function of organs (liver and kidney) is good, can satisfy the conditions of implementation chemotherapy.
  • Sign the informed consent form
  • Compliance is good, can be followed up, willing to comply with the requirements of the study

Exclusion Criteria:

  • Physical status score (ECOG) greater than 2
  • organic disease;Severely active infection;Organ transplantation immune therapy;Can't complete with in four to six cycles of chemotherapy
  • Bone marrow, liver and kidney dysfunction, clinical doctors identify intolerance to chemotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01891123

Contact: YuXiang Ma 86-020-87343786

China, Guangdong
Sun Yat-Sen University Cancer Center Recruiting
GuangZhou, Guangdong, China, 510030
Contact: YuXiang Ma    8602087343786   
Sponsors and Collaborators
Sun Yat-sen University
Principal Investigator: Li Zhang Sun Yat-sen University
Principal Investigator: Shu Sen Wang Sun Yat-sen University


Responsible Party: Li Zhang, Profressor, Sun Yat-sen University Identifier: NCT01891123     History of Changes
Other Study ID Numbers: DT0508
First Posted: July 2, 2013    Key Record Dates
Last Update Posted: December 9, 2015
Last Verified: December 2015

Keywords provided by Li Zhang, Sun Yat-sen University:
Non-small Cell Lung Cancer
Breast cancer
plasma drug concentration
Nasopharygeal carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Nose Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Skull Neoplasms
Bone Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Bone Diseases
Musculoskeletal Diseases
Nose Diseases
Otorhinolaryngologic Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action