Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Paclitaxel Detection in NSCLC Treated With TC Regimen

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.
 
ClinicalTrials.gov Identifier: NCT02737709
Recruitment Status : Terminated (The study have difficulty in recruiting subjectes)
First Posted : April 14, 2016
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Li Zhang, MD, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE March 22, 2016
First Posted Date  ICMJE April 14, 2016
Last Update Posted Date October 29, 2018
Study Start Date  ICMJE March 2016
Actual Primary Completion Date October 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2016)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02737709 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2016)
  • 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.
  • 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
  • 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.
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Paclitaxel Detection in NSCLC Treated With TC Regimen
Official Title  ICMJE 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
Brief Summary

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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE 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 Name: treatment group
Study Arms  ICMJE 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.
Intervention: Drug: Paclitaxel and Carboplatin regimen
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 25, 2018)
51
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2016)
120
Actual Study Completion Date  ICMJE October 25, 2018
Actual Primary Completion Date October 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02737709
Other Study ID Numbers  ICMJE CA139-703
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Li Zhang, MD, Sun Yat-sen University
Study Sponsor  ICMJE Sun Yat-sen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Li Zhang, M.D. Sun Yat-sen University
PRS Account Sun Yat-sen University
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP