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

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01891123
• Other study ID #: DT0508
• Status: Recruiting
• Phase: N/A
• First received: June 18, 2013
• Last updated: December 8, 2015
• Start date: June 2013
• Est. completion date: December 2016

Study information

• Verified date: December 2015
• Source: Sun Yat-sen University
• Contact: YuXiang Ma
• Phone: 86-020-87343786
• Email: mayx[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Nasal Cancer
• Non-small Cell Lung Cancer

Intervention

Device:
• PK guided arm
the dose of PTX or DOC will adjust based on the plasma drug concentration of previous cycle

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

Locations

Country	Name	City	State
China	Sun Yat-Sen University Cancer Center	GuangZhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

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* Note: There are 39 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the quality of life of patients		3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks	Yes
Primary	Toxicities rate	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.	3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18weeks	Yes
Secondary	Object response rate	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.	up to 18 weeks	Yes
Secondary	Survival Effectiveness	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.	36 months	Yes