Ignite Creation Date:
2024-05-06 @ 2:58 PM
Last Modification Date:
2024-10-26 @ 1:41 PM
Study NCT ID:
NCT04489706
Status:
UNKNOWN
Last Update Posted:
2020-07-28
First Post:
2020-07-05
Brief Title:
Arsenic Trioxide in Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation
Sponsor:
Ruijin Hospital
Organization:
Ruijin Hospital
Study Overview
Official Title:
A Clinical Trial to Evaluate the Efficacy Safety and Tolerability of Arsenic Trioxide for Injection in Patients With Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation
Status:
UNKNOWN
Status Verified Date:
2020-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is a Single-center open single-arm and non-randomized clinical trial in China The aim of this study is to evaluate the efficacy safety and tolerability of Arsenic trioxide for injection in patients with recurrent and metastatic ovarian cancer and endometrial cancer with P53 mutation A group of 20 women with histologically confirmed ovarian cancer and endometrial cancer who had previously received at least one line of standard system therapy and had relapsed or metastasized had a P53 mutation
The subjects of this study are histologically confirmed ovarian cancer and endometrial cancer patients with P53 mutation who had relapsed or metastasized after at least one line of standard system therapy 20 subjects will be enrolled in this study
Main objectives of the study are Independent imaging and tumor markers assess ORR objective response rate in patients with recurrent and metastatic ovarian cancer and endometrial cancer with P53 mutation treated with Arsenic trioxide for injection based on RECIST v11 Response evaluation criteria in solid tumors Secondary objectives including DCR Disease control rate CBR Clinical benefit rate PFS Progression free survival OS Overall survival DoR Duration of response safety and tolerability of Arsenic trioxide for injection based on NCI CTCAE National Cancer Institute Common Terminology Criteria for Adverse Events evaluated by researchers and life quality
The study will be conducted in the department of obstetrics and gynecology in Shanghai Jiaotong University School of Medicine affiliated Ruijin Hospital
Research intervention injection Arsenic trioxide 016mgkg maximum single dose is 10 mg daily IV drip d1 to d14 once every 28 days for six cycles of treatment or until one of the following events occurs Initiation of new anti-tumor therapy disease progression withdrawal of Informed consent form ICF andor death
The duration of this study will be 25 years the admission period will be 15 years and the follow-up period will be 1 year
The subjects of this study are histologically confirmed ovarian cancer and endometrial cancer patients with P53 mutation who had relapsed or metastasized after at least one line of standard system therapy 20 subjects will be enrolled in this study
Main objectives of the study are Independent imaging and tumor markers assess ORR objective response rate in patients with recurrent and metastatic ovarian cancer and endometrial cancer with P53 mutation treated with Arsenic trioxide for injection based on RECIST v11 Response evaluation criteria in solid tumors Secondary objectives including DCR Disease control rate CBR Clinical benefit rate PFS Progression free survival OS Overall survival DoR Duration of response safety and tolerability of Arsenic trioxide for injection based on NCI CTCAE National Cancer Institute Common Terminology Criteria for Adverse Events evaluated by researchers and life quality
The study will be conducted in the department of obstetrics and gynecology in Shanghai Jiaotong University School of Medicine affiliated Ruijin Hospital
Research intervention injection Arsenic trioxide 016mgkg maximum single dose is 10 mg daily IV drip d1 to d14 once every 28 days for six cycles of treatment or until one of the following events occurs Initiation of new anti-tumor therapy disease progression withdrawal of Informed consent form ICF andor death
The duration of this study will be 25 years the admission period will be 15 years and the follow-up period will be 1 year
Detailed Description:
The P53 mutation plays an important role in the development of ovarian cancer and endometrial cancer which has been found to occur in more than 95 of high grade serous ovarian cancers 25 of the endometrial cancer with serous endometrial cancer having a P53 mutation rate of 88
In Acute promyelocytic leukemia treatment a combination of retinoic acid ATRA and Arsenic trioxide ATO has an extremely high cure rate with an overall five-year survival rate of 88 the therapeutic effect of ATO on some hematologic malignancies has been widely recognized Whats more it is also found that arsenic has potential therapeutic effects on a variety of solid tumors including Esophageal liver and lymphoma
Preciously research modified H1299 cells with structural mutant P53 p53-R175H and treated them with doxcycline to knock down p53-R175H The system was able to determine whether the observed antitumor effects were dependent on the structural mutant p53 In the transplanted tumor model of this cell line in mice ATO significantly inhibited the tumor growth rate In mice fed with doxcycline cancer cells expressed almost no P53-R175H and the ATO had limited inhibitory effect on the transplanted tumor model These results suggest that ATO inhibits tumor cell proliferation mainly by targeting structural mutant p53
Researchers tested the antineoplastic effects of ATO on various solid tumor PDX models on a small scale the results showed than the antineoplastic effect of ATO on the PDX Patient-Derived tumor Xenograft model was observed in several solid tumor models with structural mutant P53 including liver Lung and Pancreatic Cancer This suggests that the antineoplastic effects of ATO are not limited to the types of cancer Its anti-tumor effect is only related to the structural mutant p53 in cancer cells
Previous studies have shown that Arsenic trioxide can bind to the structural mutant P53 and partially restore its function so the goal of this study is to observe the efficacy safety and tolerability of Arsenic trioxide for injection in patients with recurrent and metastatic ovarian cancer and endometrial cancer combined with P53 mutation
In Acute promyelocytic leukemia treatment a combination of retinoic acid ATRA and Arsenic trioxide ATO has an extremely high cure rate with an overall five-year survival rate of 88 the therapeutic effect of ATO on some hematologic malignancies has been widely recognized Whats more it is also found that arsenic has potential therapeutic effects on a variety of solid tumors including Esophageal liver and lymphoma
Preciously research modified H1299 cells with structural mutant P53 p53-R175H and treated them with doxcycline to knock down p53-R175H The system was able to determine whether the observed antitumor effects were dependent on the structural mutant p53 In the transplanted tumor model of this cell line in mice ATO significantly inhibited the tumor growth rate In mice fed with doxcycline cancer cells expressed almost no P53-R175H and the ATO had limited inhibitory effect on the transplanted tumor model These results suggest that ATO inhibits tumor cell proliferation mainly by targeting structural mutant p53
Researchers tested the antineoplastic effects of ATO on various solid tumor PDX models on a small scale the results showed than the antineoplastic effect of ATO on the PDX Patient-Derived tumor Xenograft model was observed in several solid tumor models with structural mutant P53 including liver Lung and Pancreatic Cancer This suggests that the antineoplastic effects of ATO are not limited to the types of cancer Its anti-tumor effect is only related to the structural mutant p53 in cancer cells
Previous studies have shown that Arsenic trioxide can bind to the structural mutant P53 and partially restore its function so the goal of this study is to observe the efficacy safety and tolerability of Arsenic trioxide for injection in patients with recurrent and metastatic ovarian cancer and endometrial cancer combined with P53 mutation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None