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

Primary Purpose

Non-Small Cell Lung Cancer

Status

Unknown status

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

dosage of paclitaxel

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Chemotherapy, Individual Paclitaxel dose, pharmacokinetics

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

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.

Exclusion Criteria:

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

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.

Sites / Locations

Medical Department, Shanghai Pulmonary HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

pharmacokinetics group

Body surface area(BSA) group

Arm Description

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 .

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Objective response rate

The objective tumour response rate will be calculated as the percentage of evaluable patients with complete response (CR) and partial response (PR).

Progression free survival

Progression Free Survival (PFS) is defined as the time from randomization to the first documentation of objective disease progression (PD) or death from any cause.

Overall survival

Overall survival(OS) is defined as the interval between the date of randomization and the date of patient death due to any cause, or the last date the patient was known to be alive.

Quality of life

Data on QoL will be assessed using the Functional Assessment of Cancer Therapy - Lung (FACT-L) for every patients.

Full Information

NCT ID

NCT02058433

First Posted

January 27, 2014

Last Updated

February 6, 2014

Sponsor

Caicun Zhou

1. Study Identification

Unique Protocol Identification Number

NCT02058433

Brief Title

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

2. Study Status

Record Verification Date

February 2014

Overall Recruitment Status

Unknown status

Study Start Date

January 2014 (undefined)

Primary Completion Date

December 2015 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Caicun Zhou

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Small Cell Lung Cancer

Keywords

Chemotherapy, Individual Paclitaxel dose, pharmacokinetics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

pharmacokinetics group

Arm Type

Experimental

Arm Description

Arm Title

Body surface area(BSA) group

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Other

Intervention Name(s)

dosage of paclitaxel

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

dosage of paclitaxel

Intervention Description

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.

Primary Outcome Measure Information:

Title

CTCAE grade 4 of the blood marrow

Description

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

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Objective response rate

Description

The objective tumour response rate will be calculated as the percentage of evaluable patients with complete response (CR) and partial response (PR).

Time Frame

Tumor assessment 6-8 weeks after the initiation of chemotherapy

Title

Progression free survival

Description

Progression Free Survival (PFS) is defined as the time from randomization to the first documentation of objective disease progression (PD) or death from any cause.

Time Frame

12 months

Title

Overall survival

Description

Overall survival(OS) is defined as the interval between the date of randomization and the date of patient death due to any cause, or the last date the patient was known to be alive.

Time Frame

24 months

Title

Quality of life

Description

Data on QoL will be assessed using the Functional Assessment of Cancer Therapy - Lung (FACT-L) for every patients.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For inclusion in the study treatment period patients must fulfil all of the following criteria: 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. Exclusion Criteria: Any of the following is regarded as a criterion for exclusion from the study: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jie Zhang, MD

Phone

13501878890

zhangjie2172@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Caicun Zhou, Ph.D

Organizational Affiliation

Tongji University Affiliated Shanghai Pulmonary Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical Department, Shanghai Pulmonary Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200433

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jie Zhang, MD

Phone

13501878890

zhangjie2172@163.com

First Name & Middle Initial & Last Name & Degree

Caicun Zhou, PH.D

First Name & Middle Initial & Last Name & Degree

Jie Zhang, MD

First Name & Middle Initial & Last Name & Degree

Huiwei Qi, MD

First Name & Middle Initial & Last Name & Degree

Fengying Wu, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

31077432

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.

Results Reference

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

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