Paclitaxel Detection in NSCLC Treated With TC Regimen

• Status: Terminated
• Trial end date: 2018-10-25
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Treatments: Albumin-Bound Paclitaxel; Carboplatin; Paclitaxel

Criteria

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.