Safety Study of Individual Paclitaxel Dose Adjustment Based on Pharmacokinetics in Non-Small Cell Lung Cancer (NSCLC)

NCT02058433 | Unknown Phase 3 DMC

• 1 other identifier: SPAP
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Chemotherapy; Individual Paclitaxel dose; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• CTCAE grade 4 of the blood marrow

  Record the number of CTCAE grade 4 of the blood marrow such as Leukocytes, Neutrophils,Platelets and Hemoglobin in two treatment groups since the initiation of chemotherapy

  24 months

Secondary Outcomes (4)

• Objective response rate

  Tumor assessment 6-8 weeks after the initiation of chemotherapy

• Progression free survival

  12 months

• Overall survival

  24 months

• Quality of life

  24 months

Study Arms (2)

pharmacokinetics group

EXPERIMENTAL

Based on pharmacokinetics. Observe safety and efficacy. In first cycle a fixed Paclitaxel dose depends on BSA. In subsequent cycles the dosage of Paclitaxel will be adjusted depending on pharmacokinetics follow up .

Other: dosage of paclitaxel

Body surface area(BSA) group

ACTIVE COMPARATOR

Based on body surface area. The dosage of Paclitaxel is based on the BSA of the patient. Paclitaxel/carboplatin up to 4 cycles or disease progression or intolerable toxicity.

Other: dosage of paclitaxel

Interventions

dosage of paclitaxel OTHER

Based on pharmacokinetics. Observe the toxicity in an individual patient after a fixed Paclitaxel dose depending on BSA and then the dosage of Paclitaxel is adjusted depending on pharmacokinetics follow up to avoid excess toxicity in subsequent cycles.

pharmacokinetics group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent.
• Male or female aged 18 years and over.
• Histologically or cytologically confirmed non-small cell lung carcinoma.
• Locally advanced Stage not amenable to local therapy (e.g. pleural effusion) or metastatic disease.
• 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.
• World Health Organization (WHO) performance status (PS) of 0 to 2.
• 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.
• 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
• Measurable disease according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria with at least one measurable lesion not previously irradiated.
• Life expectancy ≥12 weeks.

You may not qualify if:

• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
• Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
• 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.
• Prior treatment with paclitaxel.
• Current treatment with target drug and biological therapy.
• Pregnant or lactating woman.
• 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.
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
• Life expectancy of less than 12 weeks.
• Unable to tolerate carboplatin / paclitaxel doublet chemotherapy, as judged by the investigator.

Sponsors & Collaborators

• Caicun Zhou: lead

Study Sites (1)

Medical Department, Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 31077432 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Caicun Zhou, Ph.D

  Tongji University Affiliated Shanghai Pulmonary Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Zhang, MD

CONTACT

13501878890; zhangjie2172@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Tonji University Affiliated Shanghai Pulmonary Hospital

Study Record Dates

• First Submitted: January 27, 2014
• First Posted: February 10, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: February 10, 2014

Record last verified: 2014-02

Locations

CN (1)