Clinical trial NCT06722950: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Colorectal Adenoma
Lead sponsor: Shandong New Time Pharmaceutical Co., LTD
Sponsor class: INDUSTRY
First posted: 2024-12-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).

Eligibility criteria: Inclusion Criteria:

1. Understand the experimental procedures and contents, and voluntarily sign a written informed consent;
2. Male or female subjects aged 18 to 75 years (inclusive) when signing the informed consent;
3. 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;
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 before the first medication in the study;
5. 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.
6. Male or female subjects of fertility are required to take effective medical contraceptive measures until 3 months after the last study administration.

Exclusion Criteria:

1. 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);
2. Patients diagnosed with damp-heat syndrome or liver depression-fire syndrome according to TCM during the screening period;
3. Patients with severe diabetic peripheral neuropathy (such as muscle atrophy as the main stage) and abnormal electromyography;
4. Patients with known allergic reactions to any component of the study drug;
5. Patients with intestinal obstruction that requires treatment;
6. Active severe clinical infection (\> grade 2, National Cancer Institute-Common Adverse Event Evaluation Criteria \[NCI-CTCAE V5.0\]), including active tuberculosis;
7. 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;
8. 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);
9. Patients who need to take coumarin derivative anticoagulants (such as warfarin, phenprocoumon) regularly within 3 weeks before screening or during the study;
10. 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;
11. Renal replacement therapy;
12. Previous history of organ transplantation, autologous/allogeneic stem cell transplantation;
13. 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;
14. 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;
15. Pregnancy (confirmed by menstrual pregnancy test) or lactation;
16. Current alcohol or drug dependence;
17. Suffering from known mental illness disorders that may affect trial compliance;
18. Adverse events of previous anti-tumor treatment have not recovered to grade 1 (NCI-CTCAE V5.0) or abnormalities have no clinical significance;
19. Subjects who have participated in other interventional clinical trials within 4 weeks before the first study drug;
20. The investigator believes that the patient has other factors that affect the efficacy or safety evaluation of this study

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