Arsenic Trioxide in Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation
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|ClinicalTrials.gov Identifier: NCT04489706|
Recruitment Status : Recruiting
First Posted : July 28, 2020
Last Update Posted : July 28, 2020
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 v1.1 （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, 0.16mg/kg (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) and/or death.
The duration of this study will be 2.5 years; the admission period will be 1.5 years and the follow-up period will be 1 year.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Endometrial Cancer||Drug: Arsenic trioxide for injection||Not Applicable|
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. What's 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||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.|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||June 28, 2020|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||November 2022|
Experimental: P53 mutation arm
patients of recurrent and metastatic ovarian cancer and endometrial cancer associated with P53 mutation
Drug: Arsenic trioxide for injection
Arsenic trioxide for injection, 0.16 mg/kg (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) and/or death.
Other Name: Arsenic trioxide for injection，producted by Beijing SL Pharmaceutical Co., Ltd.
- the diameter of the measurable lesion [ Time Frame: From the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, through study completion, an average of 1 year. ]The retraction degree of the lesion which was detected in the beginning of the study (measured by CT, MRI or ultrasound).
- the level of tumor markers in serum. [ Time Frame: From the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, through study completion, an average of 1 year. ]the level of CA125 (carbohydrate antigen 125), HE4 (human epididymis protein 4) or other abnormal tumor markers in serum.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04489706
|Contact: Tianjiao Lyu, PhDemail@example.com|
|Contact: Yahui Jiang, PhDfirstname.lastname@example.org|
|Study Chair:||Weiwei Feng, PhD||Ruijin Hospital|