Phase II Clinical Study of AC591 in Preventing Oxaliplatin-Induced Peripheral Neuropathy

Official title

A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Clinical Study of AC591 in Preventing Oxaliplatin-Induced Peripheral Neuropathy

Overview

A randomized, double-blind, placebo-controlled, multicenter, Phase II clinical study of AC591 in preventing Oxaliplatin-Induced Peripheral Neuropathy

Detailed description

This multicenter, randomized, double-blind, placebo-controlled trial aims to explore the effectiveness of AC591 particles in preventing oxaliplatin-induced peripheral neuropathy. Patients with colorectal adenocarcinoma who are prepared to receive CAPEOX (capecitabine tablets + oxaliplatin injection) postoperative adjuvant chemotherapy within 3 weeks to 2 months after surgery will be randomized in a 1:1 ratio. The subjects will be stratified based on the chemotherapy cycles they are prepared to receive CAPEOX (4 cycles vs 8 cycles).

Interventions

• Drug CAPEOX
  CAPEOX: 130mg/m2 of oxaliplatin (D1, central intravenous drip for 2h (time window + 20min)), 1000mg/m2 of capecitabine tablets each time, orally, twice a day (D1-D14, morning and evening); repeat the CAPEOX chemotherapy regimen every 3 weeks.
• Drug Placebo
  Placebo：3 times a day (daily), taken with boiled water.
• Drug AC591
  AC591 : 3 times a day (daily), taken with boiled water.

Primary outcome measures

• Proportion of subjects with grade 1-3 oxaliplatin-induced peripheral neuropathy as assessed by the oxaliplatin-specific Levi rating tool [Time frame: At the end of Cycle 4 （each cycle is 21 days）]

Secondary outcome measures (10)

• Proportion of subjects with grade 1-3 oxaliplatin-induced peripheral neuropathy as assessed by the oxaliplatin-specific Levi rating tool [Time frame: At the end of Cycle 8（each cycle is 21 days）]
• The time of onset of grade 1-3 oxaliplatin-induced peripheral neuropathy assessed by the Levi rating tool for oxaliplatin [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The incidence of NCI-CTCAE V5.0 ≥ grade 2 neurotoxicity in subjects during CAPEOX chemotherapy [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The change in the EORTC-QLQ-CIPN20 score of subjects during CAPEOX chemotherapy from baseline [Time frame: at the end of each cycle（each cycle is 21 days）]
• The change in the EORTCQLQ-C30 score of subjects during CAPEOX chemotherapy from baseline [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The proportion of subjects who used analgesics due to peripheral neuropathy caused by CAPEOX chemotherapy [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The proportion of subjects who developed acute peripheral neuropathy within 3 days after the first CAPEOX chemotherapy [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The average cumulative dose of oxaliplatin received by the subjects during CAPEOX chemotherapy [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The incidence of gastrointestinal adverse reactions in the subjects during CAPEOX chemotherapy [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]
• The proportion of subjects who did not experience neurotoxicity as assessed by the Levi rating tool dedicated to oxaliplatin [Time frame: At the end of Cycle 4 and 8（each cycle is 21 days）]

Eligibility criteria

Inclusion criteria

• Understand the experimental procedures and contents, and voluntarily sign a written informed consent;
• Male or female subjects aged 18 to 75 years (inclusive) when signing the informed consent;
• Patients with histologically confirmed colorectal adenocarcinoma. Prepare to receive CAPEOX postoperative adjuvant chemotherapy within 3 weeks to 2 months after surgery, and have never used oxaliplatin;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 before the first medication in the study;
• Organ function level before the first medication in the study meets the following requirements:

Peripheral blood cell count: white blood cell count ≥3×109/L and neutrophil ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90g/L; Liver function: total bilirubin ≤1.5 times the upper limit of normal reference value; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal reference value; Renal function: serum creatinine ≤1.5 times the upper limit of normal reference value.

• Male or female subjects of fertility are required to take effective medical contraceptive measures until 3 months after the last study administration.

Exclusion criteria

• known neurodegenerative disease (e.g., Parkinson's disease, Alzheimer's disease, Huntington's disease) or neuromuscular disease (e.g., multiple sclerosis, amyotrophic lateral sclerosis, poliomyelitis, hereditary neuromuscular disease);
• Patients diagnosed with damp-heat syndrome or liver depression-fire syndrome according to TCM during the screening period;
• Patients with severe diabetic peripheral neuropathy (such as muscle atrophy as the main stage) and abnormal electromyography;
• Patients with known allergic reactions to any component of the study drug;
• Patients with intestinal obstruction that requires treatment;
• Active severe clinical infection (> grade 2, National Cancer Institute-Common Adverse Event Evaluation Criteria \[NCI-CTCAE V5.0\]), including active tuberculosis;
• Uncontrolled diabetes, severe lung disease (such as acute lung disease, pulmonary fibrosis affecting lung function, interstitial lung disease, but excluding recovered radiation pneumonia), liver failure;
• Clinically significant cardiovascular disease, New York Heart Association \[NYHA\] grade III-IV congestive heart failure, unstable angina, myocardial infarction, etc. within 6 months before the first dose. Uncontrolled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg after adequate treatment);
• Patients who need to take coumarin derivative anticoagulants (such as warfarin, phenprocoumon) regularly within 3 weeks before screening or during the study;
• Patients who have used drugs that interfere with the evaluation of neuropathic pain (such as antidepressants, antiepileptic drugs) within 2 weeks before the first dose;
• Renal replacement therapy;
• Previous history of organ transplantation, autologous/allogeneic stem cell transplantation;
• History of other malignant tumors except colorectal cancer in the past 5 years. However, cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, or early papillary thyroid carcinoma are excluded;
• HIV infection, hepatitis B surface antigen positive (and peripheral blood hepatitis B virus deoxynucleotide HBV DNA ≥ 1×104 copies/mL or ≥ 2000IU/mL), hepatitis C virus antibody positive (and peripheral blood hepatitis C virus nucleotide HCV RNA ≥ 1×103 copies/ml or ≥ 200IU/mL) or active syphilis patients;
• Pregnancy (confirmed by menstrual pregnancy test) or lactation;
• Current alcohol or drug dependence;
• Suffering from known mental illness disorders that may affect trial compliance;
• Adverse events of previous anti-tumor treatment have not recovered to grade 1 (NCI-CTCAE V5.0) or abnormalities have no clinical significance;
• Subjects who have participated in other interventional clinical trials within 4 weeks before the first study drug;
• The investigator believes that the patient has other factors that affect the efficacy or safety evaluation of this study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06722950 · NTP-AC591-001 · Shandong New Time Pharmaceutic

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗