Arsenic Trioxide for Structural p53 Mutations

Study Overview
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Brief Summary
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TP53 is the most frequently mutated gene in cancer, but these mutations remain therapeutically non-actionable. Previous study reported arsenic trioxide could rescue structural p53 mutations, endowing p53 mutations with thermostability and transcriptional activity. Under Vivo and Vitro experiments, arsenic trioxide could reactivate mutated p53 to inhibit tumor. This trial aimed to explore the efficacy and safety of arsenic trioxide in refractory cancer patients with structural p53 mutations.

Official Title
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Targeting Structural p53 Mutations With Arsenic Trioxide for Intractable Cancer

Conditions
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Arsenic Trioxide, p53 Mutations, Refractory Cancer, Intractable Cancer

Intervention / Treatment
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* Drug: Arsenic Trioxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Malignant solid tumors diagnosed histologically; Solid tumor patients have no any standard choice after multiple line of therapy; Next-generation Sequence showed TP53 mutation; Expected survival ≥ 1 month; ECOG / PS score: 0-2, and the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN); Liver ALT and AST <2.5 × ULN and if liver metastases, ALT and AST <5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min normal cardiac function obtain informed consent Exclusion Criteria: Patient still has standard treatment therapy based on NCCN guidance; Patient can not comply with research program requirements or follow-up; woman who are pregnant or breastfeeding; allergic to any drug in protocol or with contraindications; cannot understand or obey the protocol; with a history of allergies or intolerability; participate in other clinical trials meanwhile; any situations that hinder trial existed;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arsenic Trioxide<br>Arsenic Trioxide (0.16mg/kg,d1-5,ivgtt,28days as a duration) for injection | Drug: Arsenic Trioxide<br>* Refractory cancer patients without standard-of-care harboring TP53 mutation received Arsenic Trioxide Injection (0.16mg/kg,d1-5,ivgtt,28days as a duration)<br>* Other names: Arsenic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 2 months | 
| Progress Free Survival | Time from treatment beginning until disease progression | Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from treatment beginning until death from any cause | From date of treatment beginning until the date of death from any cause, through study completion, an average of 1 months | 
| Adverse Effect | Incidence of Treatment-related adverse Events | Through study completion, an average of 1 months |