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

NCT03258099 | Unknown

• 1 other identifier: 2016[1239]-1
• Study Type: observational
• Target: 2,200
• Locations: 1 country
• Sites: 7

Brief Summary

Capecitabine is one of the most active agents in the treatment of many kinds of solid tumors. However, variability in toxicity and response remains a major problem for patients receiving capecitabine. 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 capecitabine, such as diarrhea, hand-foot syndrome or anemia, were evaluated for possible relationship with pharmacogenetic polymorphisms in several pharmacogenomics 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 capecitabine in toxicities, through the pharmacogenomics research. The aim of this study is to evaluating the association genetic polymorphisms with capecitabine-based chemotherapy toxicities in chinese solid tumor patients. By detecting the gene polymorphism, investigators intend to study the pharmacokinetic/pharmacogenomics (PK-PG) correlation of capecitabine and provide scientific basis for precise medication guide for people to use capecitabine.

Conditions

Solid Tumor; Capecitabine; Drug-Related Side Effects and Adverse Reactions; Pharmacogenetics; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Incidence of severe diarrhea toxicity

  The toxicity induced by capecitabine-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.

  At 1 year

• Incidence of severe hand-foot syndrome toxicity

  The toxicity induced by capecitabine-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.

  At 1 year

Secondary Outcomes (4)

• Incidence of other severe toxicities

  At 1 year

• Genotyping

  Before chemotherapy

• The kinds of the metabolites

  Pre-dose and 3 hours after the last administration in the first cycle

• Area under the curve [AUC]

  Pre-dose and 3 hours after the last administration in the first cycle

Study Arms (2)

wild genotype

Through next generation sequencing, distinguish wild genotype of capecitabine

Genetic: detection of genotype

mutant genotype

Through next generation sequencing, distinguish mutant genotype of capecitabine

Genetic: detection of genotype

Interventions

detection of genotype GENETIC

detection of genotype by next generation sequencing

mutant genotype; wild genotype

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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;

You may not qualify if:

• 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:
• Bone marrow reserve:
• ANC≥1.5×109/L
• PLT≥100×109/L
• HGB≥10g/dL
• Hepatic:
• Bilirubin ≤ 1.5ULN
• ALT, AST ≤2.5 ULN, ≤5ULN when liver metastases are known.
• 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.
• Serious concomitant systemic disorder, including active infection, which is incompatible with the study (at the discretion of the investigator).

Sponsors & Collaborators

• Cui Yimin: lead

Study Sites (7)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Affiliated Hospital of Academy of Military Medical Sciences

Beijing, Beijing Municipality, 100071, China

Location

Fuling Center Hospital of Chongqing City

Chongqing, Chongqing Municipality, 408000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

Yantai Yuhuangding Hospital

Yantai, Shandong, 264000, China

Location

Yunnan Cancer Hospital

Kunming, Yunnan, 650118, China

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of pharmacy，M.D & Ph.D

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 23, 2017
• Study Start: December 28, 2017
• Primary Completion: October 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

CN (7)