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Status unknownNCT03258151Updated Aug 28, 2019

Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients

An observational study in Solid Tumors, Docetaxel and Drug-Related Side Effects and Adverse Reactions, sponsored by Cui Yimin. Status unknown at 6 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-08-28.

Sponsored by Cui Yimin · Observational

The sponsor has not verified this record recently (last verified Aug 2019), so the status shown — last known as Active, not recruiting — may be out of date.
Study type
Observational
Model
Cohort
Time perspective
Other
Enrollment
2,200
Ages
18 Years and older
Sex
All
01

Study summary

Taxanes are one of the most active agents in the treatment of many kinds of solid tumors, mainly including paclitaxel and docetaxel. However, variability in toxicity and response remains a major problem for patients receiving taxanes. It is general that there are many factors for individual differences of drugs in clinical application, of which genetic factors accounted for more than 20%. Toxicities of docetaxel, such as myelosuppression, neurotoxicity or mucositis, were evaluated for possible relationship with pharmacogenetic polymorphisms in several candidate gene and genome-wide association studies. Due to the levels of evidence of those studies are low and lack of sufficient research data of Chinese, it has the important significance in studying individual differences of docetaxel in toxicities, through the pharmacogenomics research.

The aim of this study is to evaluating the association genetic polymorphisms with docetaxel-based chemotherapy toxicities in chinese solid tumor patients. By detecting the gene polymorphism, investigators intend to study the pharmacokinetic/pharmacogenomics (PK-PG) correlation of docetaxel and provide scientific basis for precise medication guide for people to use docetaxel.

02

Conditions studied

  • Solid Tumors
  • Docetaxel
  • Drug-Related Side Effects and Adverse Reactions
  • Pharmacogenetics
  • Pharmacokinetics
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Chinese solid tumor patients with the treatment of docetaxel-based chemotherapy.

Inclusion criteria

  • Any native Chinese men or women at least 18 years of age;
  • Sign informed consent of the research;
  • Have a histologic or cytologic diagnosis of solid tumor;
  • Will receive docetaxel-based chemotherapy; Or patients who received docetaxel chemotherapy meet the inclusion and exclusion criteria of the research, and their clinical information is complete to obtain;
  • Male and female patients with reproductive potential must use an approved contraceptive method during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative pregnancy test within 7 days prior to study enrollment;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Have discontinued all previous therapies for cancer for at least 28 days prior to study entry, and have recovered from the acute effects of therapy.
  • Have adequate organ function, including:

    1. Bone marrow reserve:

      1. ANC≥1.5×109/L
      2. PLT≥100×109/L
      3. HGB≥10g/dL
    2. Hepatic:

      1. Bilirubin ≤ 1.5ULN
      2. ALT, AST ≤2.5 ULN, ≤5ULN when liver metastases are known
    3. Renal: Src ≤1.5mg/dl
  • Electrolytes: Patients may be entered into the study if, in the investigators' opinion, any electrolyte disorders, including K\<3.4mEq/L, Ca\<8.4mEq/L, or Mg\<1.2mEq/L, may be appropriately managed and stabilized by the time of the laboratory evaluation prior to the chemotherapy. If electrolytes have not been stabilized during this time, the patient will be discontinued from the study.
  • Have an estimated life expectancy, in the judgment of the investigator, which will permit the patient to complete the PK phase and at least 2 cycle of the evaluation of the toxicities.

Exclusion criteria

Exclusion Criteria;

  • Serious concomitant systemic disorder, including active infection, which is incompatible with the study (at the discretion of the investigator).
  • History of human immunodeficiency virus, hepatitis B, or hepatitis C infections.
  • Cardiac: Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV. It is recommended that patients with arrhythmias (persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation or bradycardia (heart rate \<50 beats per minute))be excluded at the investigator's discretion.
  • Known family history of unexplained sudden death.
  • Personal history of unexplained syncope within the last year.
  • Women who are breast feeding, lactating, or pregnant.
  • Patients with known allergies to docetaxel and its supplementary materials.
  • Drugs and herbal supplements that are known to be potent or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 are specifically excluded. Foods that are known to be potent or moderate inhibitors of CYP3A4 are also specifically excluded during the study.
  • Patients receiving herbal regimens.
  • Use of drugs with narrow therapeutic windows that are also known substrates of CYP3A4.
  • Failure for any reason to satisfy the investigator for adequate fitness to participated in the study.
04

Study design

Observational model
Cohort
Time perspective
Other
Enrollment
2,200 participants (estimated)
Patient registry
No

Groups and cohorts

  • wild genotype

    Through next generation sequencing, distinguish wild genotype of docetaxel

    Genetic: detection of genotype

  • mutant genotype

    Through next generation sequencing, distinguish mutant genotype of docetaxel

    Genetic: detection of genotype

Interventions

  • Geneticdetection of genotype

    detection of genotype by next generation sequencing

05

What researchers measure

Primary outcomes

  1. Incidence of severe hematological toxicity

    The toxicity induced by docetaxel-based chemotherapy during observation time will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Patients with grade 3-4 adverse events will be considered as having severe toxicity. At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis. Hematological toxicity includes neutropenia, leukopenia, anemia and thrombocytopenia.

    Time frame: At 1 year

Secondary outcomes

  1. Incidence of other severe toxicities

    The other toxicities induced by docetaxel-based chemotherapy during observation time, including gastrointestinal toxicity, neurotoxicity etc., will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Toxicities with grade 3-4 will be considered as severe toxicity, except for severe neurotoxicity (grade 2-3). At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis.

    Time frame: At 1 year

  2. Genotyping

    Collect blood specimen, then detect genotype by next generation sequencing.

    Time frame: Before chemotherapy

  3. The kinds of the metabolites

    Determine the metabolic profiles of docetaxel. This outcome is not applicable to patients retrospectively collected.

    Time frame: Pre-dose and 6 hours post-dose in the first cycle

  4. Area under the curve [AUC]

    Determine the AUC of docetaxel and its metabolites. This outcome is not applicable to patients retrospectively collected.

    Time frame: Pre-dose and 6 hours post-dose in the first cycle

06

Study locations

6 sites
  • Peking University First Hospital
    Beijing, Beijing 100034, China
  • Beijing Cancer Hospital
    Beijing, Beijing 100142, China
  • Affiliated Hospital of Academy of Military Medical Sciences
    Beijing, Beijing 100171, China
  • Fuling Center Hospital of Chongqing City
    Chongqing, Chongqing 408000, China
  • The First Hospital of China Medical University
    Shenyang, Liaoning 110001, China
  • The FIrst Affiliated Hospital of Wenzhou Medical University
    Wenzhou, Zhejiang 325000, China
07

Registry details

Key details

Study ID
NCT03258151
Lead sponsor
Cui Yimin
Responsible party
Cui Yimin (Director of pharmacy, M.D & Ph.D, Peking University First Hospital) — Sponsor-investigator
First posted
Aug 23, 2017
Start date
Sep 25, 2017
Primary completion
Sep 2019 (estimated)
Completion
Dec 2019 (estimated)
Last update
Aug 28, 2019

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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