Clinical trial NCT04695223: Arsenic Trioxide for Structural p53 Mutations
Official title: Targeting Structural p53 Mutations With Arsenic Trioxide for Intractable Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Arsenic Trioxide
p53 Mutations
Refractory Cancer
Intractable Cancer
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2021-01-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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;

Primary outcomes:
measure: Objective Response Rate
timeFrame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 2 months
measure: Progress Free Survival
timeFrame: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 2 months
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of treatment beginning until the date of death from any cause, through study completion, an average of 1 months
measure: Adverse Effect
timeFrame: Through study completion, an average of 1 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Medical Oncology, Shanghai Changzheng Hospital
Study officials:
References:
citation: Tang Y, Song H, Wang Z, Xiao S, Xiang X, Zhan H, Wu L, Wu J, Xing Y, Tan Y, Liang Y, Yan N, Li Y, Li J, Wu J, Zheng D, Jia Y, Chen Z, Li Y, Zhang Q, Zhang J, Zeng H, Tao W, Liu F, Wu Y, Lu M. Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. Cell Rep. 2022 Apr 12;39(2):110622. doi: 10.1016/j.celrep.2022.110622.