Arsenic Trioxide for Structural p53 Mutations

Targeting Structural p53 Mutations With Arsenic Trioxide for Intractable Cancer

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 Overview

• Status: Unknown
• Conditions: Refractory Cancer; Arsenic Trioxide; p53 Mutations; Intractable Cancer
• Intervention / Treatment: Drug: Arsenic Trioxide

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Department of Medical Oncology, Shanghai Changzheng Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arsenic Trioxide; Arsenic Trioxide (0.16mg/kg,d1-5,ivgtt,28days as a duration) for injection	Drug: Arsenic Trioxide; Refractory cancer patients without standard-of-care harboring TP53 mutation received Arsenic Trioxide Injection (0.16mg/kg,d1-5,ivgtt,28days as a duration); Other Names: As2O3; Arsenic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2021
• Primary Completion (ANTICIPATED): August 31, 2021
• Study Completion (ANTICIPATED): October 31, 2021

Study Registration Dates

• First Submitted: January 1, 2021
• First Submitted That Met QC Criteria: January 1, 2021
• First Posted (ACTUAL): January 5, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 6, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Arsenic Trioxide
• Other Study ID Numbers: ANTI-P53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No