Arsenic Trioxide in Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation

NCT04489706 | Unknown

• 1 other identifier: (2020)96
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Ovarian Cancer; Endometrial Cancer

Keywords

Arsenic Trioxide for injection; P53 mutation; Recurrent and Metastatic Cancer

Outcome Measures

Primary Outcomes (2)

• the diameter of the measurable lesion

  The retraction degree of the lesion which was detected in the beginning of the study (measured by CT, MRI or ultrasound).

  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 tumor markers in serum.

  the level of CA125 (carbohydrate antigen 125), HE4 (human epididymis protein 4) or other abnormal tumor markers in serum.

  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.

Study Arms (1)

P53 mutation arm

EXPERIMENTAL

patients of recurrent and metastatic ovarian cancer and endometrial cancer associated with P53 mutation

Drug: Arsenic trioxide for injection

Interventions

Arsenic trioxide for injection DRUG

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.

Also known as: Arsenic trioxide for injection，producted by Beijing SL Pharmaceutical Co., Ltd.

P53 mutation arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients woth ovarian cancer or endometrial cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants (or their legal Representatives/guardians) are required to sign an informed consent form, indicating that they understand the objectives of the study, necessary procedures and are willing to participate in the study.
• Women over 18 years of age with histologically confirmed recurrence or metastasis of ovarian cancer or endometrial cancer.
• Laboratory confirmed P53 Gene Mutation.
• Previously received no less than 1-line treatment in the past with disease recurrence or progression.
• Disease Recurrence or progression (based on clinical, tumor markers, or imaging findings) occurs less than 6 months after the last treatment.
• At least one measurable lesion was confirmed by independent central imaging, according to RECIST V1.1, or elevation of tumor markers.
• ECOG PS (Eastern Cooperative Oncology Group Performance Status) score 0-1
• Estimated survival time ≥12 weeks.
• Sexually active, fertile subjects and their spouses have to agree to contraception throughout the study and within 90 days of the last study drug being given.

You may not qualify if:

• Hematopoiesis or organ dysfunction (blood products, such as blood transfusions, should not be used until less than 14 days before the first dose of the drug is studied) .
• ANC (Absolute neutrophil count）\<1.5×10\^9/L.
• HGB（Hemoglobin）\< 8 g/dL.
• PLT (Platelet）\<100×10\^9/L.
• TBIL (Total bilirubin）\>1.5 × ULN（Upper limit of normal)
• AST（Aspartate transferase）and/or ALT（Alanine aminotransferase）\>3 × ULN，\>5 × ULN in subjects with liver metastases.
• Cr (Creatine) \>1.5 × ULN.
• INR (International normalized ratio)\>1.5 × ULN，aPTT (activated Partial thromboplastin time) \>1.5 × ULN, (INR is only applicable to subjects who have not received anticoagulation therapy).
• Radiation therapy less than 4 weeks before the first dose of study drug, or chemotherapy, biotherapy, endocrine therapy or small molecule targeted therapy before the first dose of study drug (elution ≥5 half-lives can be grouped).
• Toxic response to previous antitumor therapy has not yet recovered to 1 grade, according to NCI CTCAE V5.0, except for alopecia.
• Clinically significant active infection.
• Clinically significant active bleeding.
• Alcoholism or drug addiction.
• A history of clinically significant liver disease, including active viral or other hepatitis, alcohol abuse, or cirrhosis, except in subjects with a prior hepatitis which is inactive, confirmed by PCR (Polymerase chain reaction).
• HIV (Human immunodeficiency virus) infection.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Shanghai JiaoTong University School of Medicine affliated Ruijin Hospital

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

Related Publications (12)

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• Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113.

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• Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, Faderl S, O'Brien S, Wierda W, Pierce S, Brandt M, McCue D, Luthra R, Patel K, Kornblau S, Kadia T, Daver N, DiNardo C, Jain N, Verstovsek S, Ferrajoli A, Andreeff M, Konopleva M, Estrov Z, Foudray M, McCue D, Cortes J, Ravandi F. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017 Mar 9;129(10):1275-1283. doi: 10.1182/blood-2016-09-736686. Epub 2016 Dec 21.

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  PMID: 11704843 RESULT

• 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.

  PMID: 35417717 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Recurrence; Neoplasm Metastasis

Interventions

Arsenic Trioxide; Injections; Long-Term Synaptic Depression

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Weiwei Feng, PhD

  Ruijin Hospital

  STUDY CHAIR

Central Study Contacts

Tianjiao Lyu, PhD

CONTACT

008613482445868; ltj12196@rjh.com.cn

Yahui Jiang, PhD

CONTACT

008613918551061; fww12066@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 5, 2020
• First Posted: July 28, 2020
• Study Start: June 28, 2020
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2022
• Last Updated: July 28, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)