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

• ClinicalTrials.gov Identifier: NCT03258151
• Recruitment Status: Active, not recruiting
• First Posted: August 23, 2017
• Last Update Posted: August 28, 2019
• Sponsor: Cui Yimin
• Information provided by (Responsible Party): Cui Yimin, Peking University First Hospital

Tracking Information

• First Submitted Date: August 16, 2017
• First Posted Date: August 23, 2017
• Last Update Posted Date: August 28, 2019
• Actual Study Start Date: September 25, 2017
• Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 18, 2017)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 18, 2017)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
• Official Title: Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Other
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Chinese solid tumor patients with the treatment of docetaxel-based chemotherapy.

Condition

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

Intervention

Genetic: detection of genotype

detection of genotype by next generation sequencing

Study Groups/Cohorts

• wild genotype
  Through next generation sequencing, distinguish wild genotype of docetaxel
  Intervention: Genetic: detection of genotype
• mutant genotype
  Through next generation sequencing, distinguish mutant genotype of docetaxel
  Intervention: Genetic: detection of genotype

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 18, 2017): 2200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2019
• Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03258151
• Other Study ID Numbers: 2016[1239]-2
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Cui Yimin, Peking University First Hospital
• Study Sponsor: Cui Yimin
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Peking University First Hospital
• Verification Date: August 2019