Hypersensitivity Reaction
Conditions
Keywords
Oxaliplatin, skin test
Brief summary
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).
Interventions
DRUGOxaliplatin
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.
DRUGSaline (0.9% NaCl)
Inject 0.02 mL of 0.9% normal saline intradermally prior to administration of Cycle 6 or Cycle 2
Sponsors
Fujian Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
The primary endpoint and all key secondary endpoints of this study are analyzed solely based on the single experimental arm. The control group is established only for exploratory biomarker correlation analysis to evaluate the impact of skin test procedures on detection indicators. Therefore, despite the adoption of random grouping, this study is essentially a single-arm trial in terms of core design objectives and main analysis set. Since an error will be triggered if single-arm design is selected while the number of arms is set to 2, parallel design is chosen for the Interventional Study Model instead.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| sensitivity and specificity | One month after study completion | The proportion of patients with positive pre-medication skin test results among all patients who developed defined hypersensitivity reactions during the study The proportion of patients with negative pre-medication skin test results among all participants without hypersensitivity reactions during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional Diagnostic Performance Indices of Oxaliplatin Skin Test | One month after study completion | Calculate the following diagnostic indices of the oxaliplatin skin test: positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). |
| Kappa Coefficient of Agreement | One month after study completion | Evaluate the level of agreement between the oxaliplatin skin test results (positive/negative) and the clinical diagnosis of oxaliplatin-induced hypersensitivity reactions using the Cohen's Kappa coefficient. |
| Incidence and Severity of Skin Test-Related Adverse Events | Within 30 days after study completion | Record and grade all adverse events occurring within 72 hours after skin test administration according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0. |
| Correlation Between Serum Biomarkers and Skin Test Parameters | At baseline (pre-skin test) and 1 month after study completion | Analyze the correlation between serum biomarker levels and the following skin test parameters: Performance of the skin test procedure itself Skin test results (positive vs. negative) Diameter of the wheal induced by the skin test |
| Correlation Between Serum Biomarkers and Hypersensitivity Reaction Incidence | Throughout the study duration and up to 1 month after study completion | Evaluate the association between baseline and post-treatment serum biomarker levels and the incidence of protocol-defined oxaliplatin-induced hypersensitivity reactions. |
Countries
China
Contacts
CONTACTRongbo Lin
Outcome results
None listed