A Prospective Study on the Clinical Value of Skin Test for Oxaliplatin Hypersensitivity Reaction and Its Correlation With Biomarkers

Обзор

This is a prospective clinical study enrolling eligible subjects scheduled to receive oxaliplatin-based chemotherapy after signing informed consent forms. Subjects are randomly assigned to two groups. Group 1 (skin test group) receives an intradermal injection of 0.02 mL oxaliplatin solution (0.01-5.00 mg/mL) before cycles 6-10 (oxaliplatin-naive patients) or cycles 2-6 (patients with recurrence after adjuvant oxaliplatin chemotherapy), with a simultaneous self-negative control (0.02 mL 0.9% normal saline). A total of 1650 person-times will be included. Group 2 (negative control group) includes 50 subjects who receive 0.02 mL 0.9% normal saline intradermally before cycle 6 or 2. Assessments include: 1. Skin test results evaluated 15-30 minutes post-injection; a positive result is defined as a wheal ≥5 mm with surrounding erythema 2. Maximum diameter of skin test rash measured 15-30 minutes post-injection 3. Biomarker detection at three time points: pre-initial skin test, 1 hour post-skin test, and 1 hour post-first medication (carboxypeptidase A3, 9α,11β-PGF2, cysteinyl leukotrienes LTC4/LTD4/LTE4, IL-4/5/1β/6/8, TNF-α, MCP-1, mast cell chymase, total tryptase, ΔTryptase, ΔIL-6 peak); pre-skin test assessments include basophil activation rate, total IgE, LDH, lymphocytes, monocytes, and eosinophils 4. Occurrence, onset time, severity (graded per NCI-CTCAE Version 5.0), and classification of oxaliplatin infusion-related hypersensitivity reactions Follow-up continues until cycle 10 (cycle 6 for oxaliplatin re-exposed patients) or the first occurrence of: hypersensitivity reaction, disease progression requiring new anti-tumor therapy, intolerable toxicity, consent withdrawal, loss to follow-up, death, or other protocol-specified termination conditions. The negative control group is exclusively used for exploratory biomarker correlation analysis to assess the impact of skin test procedures, and is excluded from primary (sensitivity, specificity) and secondary (predictive values, likelihood ratios, Kappa coefficient) endpoint analyses. Limitations of this exploratory analysis are explicitly stated. Biomarker correlation analysis uses first skin test baseline data from 50 subjects per group (total 100 randomized cases). Variable block stratified randomization is performed, stratified by oxaliplatin-naive status and presence of comorbidities (diabetes, hypertension, renal insufficiency).

Вмешательства

• Препарат Oxaliplatin
  Administer 0.02 mL of oxaliplatin solution at 0.01-5.00 mg/mL intradermally before cycles 6 to 10 for oxaliplatin-naive patients, or before cycles 2 to 6 for patients with recurrent disease after adjuvant oxaliplatin chemotherapy. Meanwhile, conduct self-negative control via intradermal injection of 0.02 mL 0.9% normal saline.
• Препарат Saline (0.9% NaCl)
  Inject 0.02 mL of 0.9% normal saline intradermally prior to administration of Cycle 6 or Cycle 2

Первичные конечные точки

• sensitivity and specificity [Срок оценки: One month after study completion]

Вторичные конечные точки (5)

• Additional Diagnostic Performance Indices of Oxaliplatin Skin Test [Срок оценки: One month after study completion]
• Kappa Coefficient of Agreement [Срок оценки: One month after study completion]
• Incidence and Severity of Skin Test-Related Adverse Events [Срок оценки: Within 30 days after study completion]
• Correlation Between Serum Biomarkers and Skin Test Parameters [Срок оценки: At baseline (pre-skin test) and 1 month after study completion]
• Correlation Between Serum Biomarkers and Hypersensitivity Reaction Incidence [Срок оценки: Throughout the study duration and up to 1 month after study completion]

Критерии участия

Критерии включения

• Aged 18 years or older.
• Patients scheduled to receive oxaliplatin-containing chemotherapy during the study.
• Treatment-naive patients to oxaliplatin are eligible. Patients who may resume oxaliplatin treatment after prior adjuvant oxaliplatin chemotherapy can be enrolled as assessed by investigators.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2. Estimated survival time of no less than 3 months.
• No contraindications to oxaliplatin chemotherapy.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization, and agree to use effective contraception throughout the study and for 3 months after the last dose. Male subjects with childbearing potential female partners shall adopt reliable contraceptive measures during the study and within 3 months after final administration. Lactating women are excluded.
• Subjects fully understand the study, voluntarily sign written informed consent, and are willing and able to comply with scheduled visits, treatment regimens, laboratory tests and other study procedures.

Критерии исключения

• Received systemic steroid therapy exceeding 10 mg prednisone equivalent daily or other immunosuppressants within 21 days prior to enrollment; topical steroids applied to skin test area within 7 days before enrollment; anti-IL-6 monoclonal antibodies such as tocilizumab within 3 months prior to enrollment; anti-IgE monoclonal antibodies such as omalizumab within 6 months prior to enrollment.
• Any unresolved toxicity from previous treatment not recovered to Grade 0 or 1 per NCI CTCAE Version 6.0 before enrollment, excluding alopecia and clinically insignificant asymptomatic laboratory abnormalities.
• Known hypersensitivity to oxaliplatin or other platinum agents, ingredients and excipients of combined chemotherapeutic drugs.
• Grade 2 or higher peripheral neuropathy prior to initial medication.
• Active autoimmune diseases requiring systemic treatment with immunomodulators, corticosteroids or immunosuppressants. Replacement therapies including thyroxine, insulin and physiological corticosteroids for adrenal or pituitary insufficiency are permitted.
• Uncontrolled complications, including persistent active infection or fever ≥38℃; psychiatric or social disorders that may impair study compliance, increase adverse event risks or compromise the capacity to provide informed consent.
• Treatment with any investigational drug or participation in other clinical trials within 28 days before randomization. Enrollment is allowed if the investigational drug is deemed not to affect skin test results and relevant indicators by investigators.
• Clinically significant underlying diseases judged by investigators to interfere with drug administration or protocol compliance.
• Pregnant or breastfeeding females.
• Other subjects deemed ineligible by investigators.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Китай · 1 центр

• Fujian Cancer Hospital — Фучжоу

Идентификаторы

NCT: NCT07613905 · SYLT-034

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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