Targeting Structural p53 Mutations With Arsenic Trioxide for Intractable Cancer
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Shanghai Changzheng Hospital
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Progress Free Survival
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
Arms & Interventions
Arsenic Trioxide
Arsenic Trioxide (0.16mg/kg,d1-5,ivgtt,28days as a duration) for injection
Intervention: Arsenic Trioxide (Drug)
Outcomes
Primary Outcomes
Progress Free Survival
Time Frame: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 2 months
Time from treatment beginning until disease progression
Objective Response Rate
Time Frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 2 months
Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission
Secondary Outcomes
- Adverse Effect(Through study completion, an average of 1 months)
- Overall Survival(From date of treatment beginning until the date of death from any cause, through study completion, an average of 1 months)
Investigators
Yuan-Sheng Zang
Department Director
Shanghai Changzheng Hospital