To Study the Individual Variants of Chemotherapy-Induced Neurotoxicity

Integrating Clinical and Genomic Profiles for Prediction and Prevention of Chemotherapy-induced Neuropathy Via Big Bio-Data Analytics

To study the risk prediction of chemotherapy-induced peripheral neuropathy (CIPN) by the clinical bioinformatics and genomic profile.

Study Overview

• Status: Active, not recruiting
• Conditions: Neurotoxicity Syndromes
• Intervention / Treatment: Other: Questionnaires; Procedure: Peripheral nervous system examination; Genetic: Whole Genome Sequence

Detailed Description

This is a prospective, observational, cohort study, monitoring the chemotherapy-induced peripheral neurotoxicity by traditional clinical scales, neurological examinations, and semi-quantitative assessments. Moreover, all the genetic changes will be analyzed by next generation sequencing and we will try to identify relevant variants in individuals who suffer from chemotherapy-induced neurotoxicity.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Total 300 cancer patients will be enrolled in National Cheng Kung University Hospital from March, 2015 to March, 2017. The subjects are stage I-IV ovarian cancer patients receiving chemotherapy Paclitaxel/Carboplatin, stage II-IV endometrial cancer patients receiving chemotherapy Paclitaxel/Carboplatin, stage III & high risk stage II colorectal cancer patients receiving chemotherapy with mFOLFOX.

Description

Inclusion Criteria:

1. Histologically confirmed epithelial ovarian cancer, endometrial cancer or adenocarcinoma of colon or rectum
2. Pathological stage I~IV for ovarian cancer, stage II~IV endometrial cancer or stage III & high risk stage II for colorectal cancer
3. Scheduled to receive adjuvant Paclitaxel/Carboplatin for ovarian or endometrial cancer, or mFOLFOX6 for colorectal cancer
4. Age ≥ 20 years old
5. ECOG Performance status 0-1

6. Adequate organ function

   Bone marrow:

   Absolute neutrophil count (ANC) ≥ 1.5 x 109/L WBC ≥ 3.0 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL

   Hepatic:

   Total bilirubin level ≤ 1.0 x UNL AST and ALT ≤ 3.0 x UNL

   Renal:

   Creatinine level ≤ 1.5 mg/dL in men, ≤1.4 mg/dL in women; or Estimated CCr ≥ 60 mL/min (CCr is estimated by Cockcroft-Gault formula, as appendix III).

7. Negative pregnancy test for women of childbearing potential only
8. Patient willing to provide blood sample for research purposes
9. Written informed consent

Exclusion Criteria:

1. Prior treatment with neurotoxic chemotherapy, such as oxaliplatin, cisplatin, carboplatin, taxanes or vinca alkaloids
2. Receiving chemotherapy within 6 months
3. History of allergy to 5-FU or LV
4. Pre-existing peripheral neuropathy of any grade
5. A family history of a genetic or familial neuropathy
6. Active uncontrolled infection
7. Significant medical diseases, such as unstable angina, acute or recent myocardial infarction (<6 months before enrollment), COPD with frequent exacerbation, uncontrolled hypertension, ore cent CVA (<6 months before enrollment)
8. Poor compliance

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cancer patients receiving chemotherapy; Stage I-IV ovarian cancer receiving chemotherapy Paclitaxel/Carboplatin Stage II-IV endometrial cancer receiving chemotherapy Paclitaxel/Carboplatin Stage III & high risk stage II colorectal cancer receiving chemotherapy with mFOLFOX; Questionnaires; Peripheral nervous system examination; Whole Genome Sequence	Other: Questionnaires; EORTC CIPN20 and EQ-5D-3L; Procedure: Peripheral nervous system examination; nerve conduction velocity (NCV), quantitative sensory test (QST), and nerve excitability test (NET); Genetic: Whole Genome Sequence; Genetic Test : 10 mL blood will be collected in Blood Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events occurring after chemotherapy based on genomic profiling	up to 2 years after chemotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in quality-of-life measured by EORTC CIPN20	up to 2 years after chemotherapy
Changes in quality-of-life measured by EQ-5D-3L	up to 2 years after chemotherapy
Change from Baseline in nerve conduction velocity (NCV)	up to 2 years after chemotherapy
Change from Baseline in quantitative sensory test (QST)	up to 2 years after chemotherapy
Change from Baseline in nerve excitability test (NET)	up to 2 years after chemotherapy
Relapse-free survival	up to 5 years after chemotherapy
Overall Survival	up to 5 years after chemotherapy

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Investigators: Study Chair: Meng-Ru Shen, PHD, National Cheng Kung University

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Chemotherapy; Peripheral Neuropathy
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Poisoning; Neurotoxicity Syndromes
• Other Study ID Numbers: A-ER-103-395

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED