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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Sun Yat-sen University
Information provided by (Responsible Party):
Li Zhang, Sun Yat-sen University
ClinicalTrials.gov Identifier:
First received: June 18, 2013
Last updated: August 26, 2015
Last verified: August 2015

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 Intervention
Non-small Cell Lung Cancer
Breast Cancer
Nasal Cancer
Device: PK guided arm
Drug: PTX 175mg/m2, DOC 75mg/m2

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 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.

Resource links provided by NLM:

Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:
  • Toxicities rate [ Time Frame: 3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks ] [ Designated as safety issue: Yes ]
    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:
  • Object response rate [ Time Frame: up to 18 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Survival Effectiveness [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    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:
  • the quality of life of patients [ Time Frame: 3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: June 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed by pathology for advanced lung cancer, suitable for paclitaxel or docetaxel chemotherapy (independent of clinical stage or chemotherapy type)
  • At least one measurable lesions (according to RECIST criteria)
  • 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
  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: NCT01891123

Contact: YuXiang Ma 86-020-87343786 mayx@sysucc.org.cn

China, Guangdong
Sun Yat-Sen University Cancer Center Recruiting
GuangZhou, Guangdong, China, 510030
Contact: YuXiang Ma    8602087343786    mayx@sysucc.org.cn   
Sponsors and Collaborators
Sun Yat-sen University
Principal Investigator: Li Zhang Sun Yat-sen University
Principal Investigator: Shu Sen Wang Sun Yat-sen University
  More Information


Responsible Party: Li Zhang, Profressor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT01891123     History of Changes
Other Study ID Numbers: DT0508
Study First Received: June 18, 2013
Last Updated: August 26, 2015
Health Authority: China: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Lung Neoplasms
Breast Diseases
Bronchial Neoplasms
Neoplasms by Site
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Lung Diseases
Respiratory Tract Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 13, 2015