Clinical trial NCT02058433: Safety Study of Individual Paclitaxel Dose Adjustment Based on Pharmacokinetics in Non-Small Cell Lung Cancer (NSCLC)
Official title: Phase 3, Randomized, Open-label Study of the Safety of Individual Paclitaxel Dose Adjustment Based on Pharmacokinetic Follow up Versus Conventional Dosage in First-line Treatment in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Chemotherapy
Individual Paclitaxel dose
pharmacokinetics
Lead sponsor: Tongji University
Sponsor class: OTHER
First posted: 2014-02-10
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Platinum-based doublets including paclitaxel, gemcitabine, or docetaxel are standard 1st regimens in Non-Small Cell Lung Cancer(NSCLC). The traditional method of individualizing cytotoxic drug dose is by using body surface area(BSA), which is not correlated with the ability of an individual to metabolize or excrete cytotoxic drugs, because it is not related to liver function and is poorly correlated with glomerular filtration rate, and does not seem to be a determinant of toxicity. Pharmacokinetic parameters such as area under the curve have been shown to correlate with toxicity. The advantages of using a fixed dose of antineoplastic agents for all of the patients are obvious. Pharmacokinetically guided treatment would avoid severe adverse effects, which has not been sufficiently investigated in advanced NSCLC.First, the investigators monitor the blood concentrations of paclitaxel and neutropenia blood toxicity after chemotherapy with paclitaxel and carboplatin in patients of NSCLC and verify suitable paclitaxel therapeutic window for Chinese patients. Then the investigators compare safety and efficacy between individual paclitaxel dose adjustment based on the therapeutic window compared with conventional dosage.

Detailed description: Primary end point: Common Terminology Criteria for Adverse Events(CTCAE) grade 4.

Secondary end point:Objective Response Rate(ORR),Progression Free Survival(PFS),Overall Survival(OS),Quality Of Life(QOL) etc.

Eligibility criteria: Inclusion Criteria:

For inclusion in the study treatment period patients must fulfil all of the following criteria:

1. Provision of informed consent.
2. Male or female aged 18 years and over.
3. Histologically or cytologically confirmed non-small cell lung carcinoma.
4. Locally advanced Stage not amenable to local therapy (e.g. pleural effusion) or metastatic disease.
5. No prior chemotherapy, biological (including targeted therapies such as Epidermal Growth Factor Receptor(EGFR) and Vascular Epidermal Growth Factor (VEGF) inhibitors) or immunological therapy. Patients who are willing to accept with paclitaxel and carboplatin as adjuvant chemotherapy will be eligible.
6. World Health Organization (WHO) performance status (PS) of 0 to 2.
7. Females of child-bearing potential must have negative serum pregnancy test. Sexually active males and females (of childbearing potential) willing to practice contraception during the study.
8. Laboratory values within the range, as defined below, within two weeks of randomization:

   * Absolute neutrophils count(ANC)≥2.0×109/L
   * Platelets≥100×109/L
   * Serum bilirubin≤2×ULN; Aspartate transaminase(AST) and alanine tansaminase (ALT) ≤2.5×ULN(≤5×ULN if liver metastases)
   * Creatinine clearance≥60ml/min
9. Measurable disease according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria with at least one measurable lesion not previously irradiated.
10. Life expectancy ≥12 weeks.

Exclusion Criteria:

Any of the following is regarded as a criterion for exclusion from the study:

1. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
2. Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
3. Known severe hypersensitivity to carboplatin, paclitaxel or any of the excipients of these products.Known severe hypersensitivity to pre-medications required for treatment with carboplatin / paclitaxel doublet chemotherapy.
4. Prior treatment with paclitaxel.
5. Current treatment with target drug and biological therapy.
6. Pregnant or lactating woman.
7. Prior chemotherapy, biological (including targeted therapies such as Epidermal Growth Factor Receptor(EGFR) and Vascular Epidermal Growth Factor (VEGF) inhibitors) or immunological therapy were received even if treatment was not paclitaxel and was completed in 4 weeks before day1 of study treatment.
8. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
9. Life expectancy of less than 12 weeks.
10. Unable to tolerate carboplatin / paclitaxel doublet chemotherapy, as judged by the investigator.

Primary outcomes:
measure: CTCAE grade 4 of the blood marrow
timeFrame: 24 months
Secondary outcomes:
measure: Objective response rate
timeFrame: Tumor assessment 6-8 weeks after the initiation of chemotherapy
measure: Progression free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 24 months
measure: Quality of life
timeFrame: 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Medical Department, Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
affiliation: Tongji University Affiliated Shanghai Pulmonary Hospital
name: Caicun Zhou, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang J, Zhou F, Qi H, Ni H, Hu Q, Zhou C, Li Y, Baburina I, Courtney J, Salamone SJ. Randomized study of individualized pharmacokinetically-guided dosing of paclitaxel compared with body-surface area dosing in Chinese patients with advanced non-small cell lung cancer. Br J Clin Pharmacol. 2019 Oct;85(10):2292-2301. doi: 10.1111/bcp.13982. Epub 2019 Jun 14.