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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Ca

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.

Detailed Summary: 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 teleph
Sponsor: Sun Yat-sen University

Current Primary Outcome: 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.


Original Primary Outcome: The objective response rate [ Time Frame: up to 18 weeks ]

participants will be evaluated for response of treatment after 2 cycles,4 cycles and 6 cycles. 3weeks per cycle, so the expected time frame will be 6/12/18 weeks


Current Secondary Outcome:

  • 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.
  • 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.


Original Secondary Outcome:

  • progression free survival; overall survival [ Time Frame: 24 months ]
  • Incidence and severity of adverse reactions [ Time Frame: 3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks ]
    participants will be evaluated for adverse reactions of treatment every cycle. 3 weeks per cycle, so the expected time frame will be 3/6/9/12/15/18 weeks


Information By: Sun Yat-sen University

Dates:
Date Received: June 18, 2013
Date Started: June 2013
Date Completion: December 2016
Last Updated: December 8, 2015
Last Verified: December 2015