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

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ClinicalTrials.gov Identifier: NCT03258151
Recruitment Status : Recruiting
First Posted : August 23, 2017
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
Cui Yimin, Peking University First Hospital

Brief 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.


Condition or disease Intervention/treatment
Solid Tumors Docetaxel Drug-Related Side Effects and Adverse Reactions Pharmacogenetics Pharmacokinetics Genetic: detection of genotype

Study Type : Observational
Estimated Enrollment : 2200 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
Actual Study Start Date : September 25, 2017
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Group/Cohort Intervention/treatment
wild genotype
Through next generation sequencing, distinguish wild genotype of docetaxel
Genetic: detection of genotype
detection of genotype by next generation sequencing

mutant genotype
Through next generation sequencing, distinguish mutant genotype of docetaxel
Genetic: detection of genotype
detection of genotype by next generation sequencing




Primary Outcome Measures :
  1. Incidence of severe hematological toxicity [ Time Frame: At 1 year ]
    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.


Secondary Outcome Measures :
  1. Incidence of other severe toxicities [ Time Frame: At 1 year ]
    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.

  2. Genotyping [ Time Frame: Before chemotherapy ]
    Collect blood specimen, then detect genotype by next generation sequencing.

  3. The kinds of the metabolites [ Time Frame: Pre-dose and 6 hours post-dose in the first cycle ]
    Determine the metabolic profiles of docetaxel. This outcome is not applicable to patients retrospectively collected.

  4. Area under the curve [AUC] [ Time Frame: Pre-dose and 6 hours post-dose in the first cycle ]
    Determine the AUC of docetaxel and its metabolites. This outcome is not applicable to patients retrospectively collected.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Chinese solid tumor patients with the treatment of docetaxel-based chemotherapy.
Criteria

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;

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03258151


Contacts
Contact: Qian Xiang, Ph.D +86 010 66110802 xiangqz@126.com

Locations
China, Beijing
Peking University First Hospital Recruiting
Beijing, Beijing, China, 100034
Contact: Qiang Xiang, Ph.D    +86 010 66110802    xiangqz@126.com   
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Jun Zhao, MD         
Affiliated Hospital of Academy of Military Medical Sciences Not yet recruiting
Beijing, Beijing, China, 100171
Contact: Zefei Jiang, MD         
China, Chongqing
Fuling Center Hospital of Chongqing City Recruiting
Chongqing, Chongqing, China, 408000
Contact: Qi Zhou, MD         
China, Liaoning
The First Hospital of China Medical University Not yet recruiting
Shenyang, Liaoning, China, 110001
Contact: Yunpeng Liu, MD         
China, Zhejiang
The FIrst Affiliated Hospital of Wenzhou Medical University Recruiting
Wenzhou, Zhejiang, China, 325000
Contact: Ouchen Wang, MD         
Sponsors and Collaborators
Cui Yimin

Responsible Party: Cui Yimin, Director of pharmacy, M.D & Ph.D, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT03258151     History of Changes
Other Study ID Numbers: 2016[1239]-2
First Posted: August 23, 2017    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action