Paclitaxel Detection in NSCLC Treated With TC Regimen

October 25, 2018 updated by: Li Zhang, MD, Sun Yat-sen University

A Clinical Experience Trial to Detect the Plasma Paclitaxel Drug Concentration in Chinese Non -Small Cell Lung Cancer (NSCLC) Patients Treated With a Paclitaxel Plus Carboplatin (TC) Regimens, and Explore Individualized Treatment Using Pharmacokinetically-guided Dosing Strategy

By detecting the blood concentration of paclitaxel (PTX), Investigator assume this research can identify the individual differences of PTX pharmacokinetics (PK) parameters (TC>0.05 refers to the duration of paclitaxel plasma concentration above 0.05 µmol/L) in Chinese non-small cell lung cancer (NSCLC) patients, and find the correlation between PK results and PTX toxicities and Effectiveness, acquire the optimization method of PTX, and finally try to explore the individualized PTX pharmacokinetically-guided dosing strategy. Orally administer rosiglitazone, which is a substrate of CYP2C8 the same as paclitaxel, before chemotherapy injection. Detect the blood concentration of rosiglitazone, analyze the correlation of rosiglitazone pharmacokinetic parameter and paclitaxel exposure, and explore the effect of rosiglitazone as an in vivo probe of paclitaxel exposure.

  1. The variability of paclitaxel concentrations in the patient population dosed by body surface area (BSA), and the limitation of BSA-based dosing of paclitaxel.
  2. Verify that paclitaxel TC>0.05 is the most relevant predictor of haematological toxicity and clinical outcomes.
  3. Define a dosing algorithm based on paclitaxel TC>0.05 of paclitaxel and 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 measurement.
  5. Construct a trial outline with the aim of reducing grade 4 neutropenia toxicity and ensuring the clinical outcome by using individual dose adjustments based on the dosing algorithm.
  6. Detect the blood concentration of rosiglitazone after orally administration, explore the effect of rosiglitazone as an in vivo probe of paclitaxel exposure based on CYP2C8 activity. Attempt to establish a model to predict the paclitaxel exposure of patients base on rosiglitazone blood concentration before chemotherapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Rosiglitazone probe:

Rosiglitazone: time point - at least 20 hours before the initiation of chemotherapy, orally administrate 2mg rosiglitazone.

Only before the first cycle chemotherapy.

Chemotherapy regimen:

Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection. 21 days per cycle; 6 cycles in total.

Blood samples collection design:

  1. Rosiglitazone blood sample:

    Only one blood sample before 1st cycle:

    - Sample collected 3 hours after orally administration of rosiglitazone, with EDTA blood tube, at least 4ml;

  2. Paclitaxel blood samples:

Two blood samples per cycle:

  • Sample collected before PTX, with EDTA blood tube, at least 2ml;
  • Sample collected 24 hours after the initiation of PTX, with EDTA blood tube, at least 2ml;

Primary Objective:

Object response rate (ORR): assess the ORR of paclitaxel/carboplatin chemotherapy according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, and analyze the relationship of paclitaxel TC>0.05 and ORR.

Secondary Objectives:

Pharmacokinetic parameters: detect the blood concentration of paclitaxel 24 hours after the initiation, and the blood concentration of rosiglitazone 3 hours after orally administration of rosiglitazone. Calculate paclitaxel TC>0.05 and analyze the correlation of rosiglitazone concentration and paclitaxel TC>0.05.

Toxicities rate: assess the toxicities rate and severity of paclitaxel/carboplatin chemotherapy according to Common Terminology Criteria For Adverse Events (CTCAE) v4.03, and analyze the relationship of paclitaxel TC>0.05 and toxicities.

Survival Effectiveness: assess the progression free survival (PFS) and overall survival (OS) of paclitaxel/carboplatin chemotherapy, analyze the relationship of paclitaxel TC>0.05 and survival Effectiveness.

A single arm, phase II, monocentric, clinical experience trial. The eligible patients sign a informed consent form, and receive a 4 - 6 cycles of paclitaxel/carboplatin chemotherapy. 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.

Response follow-up: 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.

Toxicities follow-up: record the toxicities incident and grades from the first cycle to last cycle until the toxicities relieve or stabilize.

Survival follow-up: 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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-Sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age: 18 ~75 years
  • Pathology: Confirmed by pathology (histology or cytology) for advanced non-small cell lung cancer
  • Have indications of paclitaxel/carboplatin chemotherapy, suitable for paclitaxel chemotherapy (independent of clinical tumor stage or chemotherapy type or palliative chemotherapy lines)
  • At least one measurable tumor lesions (according to RECIST 1.1 criteria)
  • ECOG PS score: 0 to 2 points
  • Life expectancy: more than 3 months
  • Bone marrow reserve function is good, the function of organs (liver and kidney) is good, can satisfy the conditions of implementation chemotherapy. neutrophil count ≥1.5×109/l, platelet ≥75×109/l, hemoglobin >9g/dl, Total Bilirubin ≤1.5×ULN*, transaminase <2.5×ULN*, creatinine ≤1.5×ULN*,or creatinine clearance rate ≥45ml/min. ULR: Upper Limit Of Normal.
  • Sign the informed consent form; Compliance is good, can be followed up, willing to comply with the requirements of the study

Exclusion Criteria:

  • ECOG Performance Scores > 2 points
  • Organic disease (heart, liver, kidney disease etc), Active infection Organ transplantation immunosuppressive therapy, not capable to complete 4 - 6 cycles of paclitaxel / carboplatin chemotherapy.
  • Any other tumor history not cured in 3 years before this trial.
  • Bone marrow function or organs function not eligible for chemotherapy.
  • Diabetic patients currently receiving the standard anti- diabetes treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Paclitaxel and Carboplatin regimen
Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection. 21 days per cycle; 6 cycles in total.
Drug: Paclitaxel and Carboplatin regimen
Chemotherapy regimen:Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S；Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection.
Other Names:
  • treatment group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of tumor sizes from baseline
Time Frame: baseline; 6 weeks; 12 weeks; 18 weeks; 24 weeks; 32 weeks; up to 3 years.
Object response rate (ORR): assess the ORR of paclitaxel/carboplatin chemotherapy according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
baseline; 6 weeks; 12 weeks; 18 weeks; 24 weeks; 32 weeks; up to 3 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration versus time curve (AUC) of rosiglitazone
Time Frame: 3 hours after rosiglitazone administration
Detect the plasma concentration of rosiglitazone 3 hours after orally administration of rosiglitazone.
3 hours after rosiglitazone administration
The duration of paclitaxel plasma concentration above 0.05 µmol/L (TC>0.05)
Time Frame: 5min before paclitaxel administration; and 24 hours after.
Detect the blood concentration of paclitaxel 24 hours after the initiation, Calculate paclitaxel TC>0.05
5min before paclitaxel administration; and 24 hours after.
Toxicities rate
Time Frame: day10, day21, day 31, day 42, day 52, day 63, day 73, day 84, day 94, day 105, day115 and day 126.
Toxicities rate: assess the toxicities rate and severity of paclitaxel/carboplatin chemotherapy according to Common Terminology Criteria For Adverse Events (CTCAE) v4.03, and analyze the relationship of paclitaxel TC>0.05 and toxicities.
day10, day21, day 31, day 42, day 52, day 63, day 73, day 84, day 94, day 105, day115 and day 126.
progression free survival (months)
Time Frame: From date of consent form until the date of first documented progression, up to 36 months.
Survival Effectiveness: assess the progression free survival (PFS) of paclitaxel/carboplatin chemotherapy
From date of consent form until the date of first documented progression, up to 36 months.
Overall survival (months)
Time Frame: From date of consent form until the date of death from any cause, up to 36 months.
Survival Effectiveness: assess the overall survival (OS) of paclitaxel/carboplatin chemotherapy
From date of consent form until the date of death from any cause, up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Li Zhang, M.D., Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2016

Primary Completion (Actual)

October 25, 2018

Study Completion (Actual)

October 25, 2018

Study Registration Dates

First Submitted

March 22, 2016

First Submitted That Met QC Criteria

April 9, 2016

First Posted (Estimate)

April 14, 2016

Study Record Updates

Last Update Posted (Actual)

October 29, 2018

Last Update Submitted That Met QC Criteria

October 25, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA139-703

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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