Niraparib Combined With Brivanib or Toripalimab in Patients With Cervical Cancer

NCT04395612 | Unknown Phase 2

• 1 other identifier: CQGOG0101
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

A Clinical Proof-of-concept Study Evaluating Efficacy and Safety of ZL-2306 (Niraparib) Combined With Brivanib or Toripalimab in Patients With Metastatic, Recurrent, and Persistent Cervical Cancer

Conditions

Cervical Cancer

Keywords

Cervical Cancer,Niraparib,Brivanib,Toripalimab

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective To evaluate the objective response rate (CR + PR) of ZL-2306 (niraparib) combined with brivanib or toripalimab in patients with relapsed and persistent cervical cancer.

  6 months

Secondary Outcomes (2)

• PFS

  6 months

• DCR

  6 months

Study Arms (2)

Treatment arm1

EXPERIMENTAL

niraparib 200mg/day and brivanib 400mg/day

Drug: niraparib combined with brivanib

Treatment arm2

EXPERIMENTAL

niraparib 200mg/day and toripalimab 240mg/21 days

Drug: niraparib combined with toripalimab

Interventions

niraparib combined with brivanib DRUG

Drug：Niraparib will be administered as a dose of 200 mg orally every day. Drug：Brivanib will be administered as a dose of 400mg orally every day.

Also known as: Treatment group1

Treatment arm1

niraparib combined with toripalimab DRUG

Drug：Niraparib will be administered as a dose of 200 mg orally every day. Drug：Toripalimab will be administered as a dose of 240mg Intravenously every 21days.

Also known as: Treatment group2

Treatment arm2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, aged ≥ 18 yrs and ≤70 yrs;
• Patients volunteered to participate in this study, signed informed consent, good compliance, and cooperated with follow-up;
• The subjects' damage caused by other treatments has been recovered (NCI CTCAE version 5.0 grade ≤ grade 1), ECOG score ≤ 2 points
• Expected survival is longer than 3 months;
• Pathological diagnosis of cervical squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma;
• Evaluable lesions: CT scan of tumor lesions ≥5mm in length, CT scan of lymph node lesions ≥10mm in length, and scan layer thickness not greater than 5mm (refer to RECIST 1.1);
• The first diagnosis was confirmed by pathology and / or cytology to be metastatic, or recurrent, persistent cervical cancer (mainly refers to tumors remaining or progressing at least 3 months after initial radiotherapy or concurrent chemoradiotherapy), and the patient can no longer accept Surgery or chemoradiation;
• Subject agrees to take blood sample;
• Subjects can provide formalin-fixed, paraffin-embedded tumor tissue samples for subsequent related gene testing (optional);
• A.Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.0×109/L ; platelets \>=100×109/L B. Biochemical test standards: a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 times the upper limit of normal value (ULN). If with liver metastases, ALT and AST ≤ 5 × ULN; b. Total bilirubin (TBIL) ≤ 1.5 × ULN; c. Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 60ml / min; d. Doppler ultrasound evaluation: left ventricular ejection Blood fraction (LVEF) ≥ the lower limit of normal value (50%).
• Women of childbearing age should agree that contraception (such as an intrauterine device, contraceptive, or condom) must be used during the study and within 3 months after the last dose; a serum or urine pregnancy test must be negative within 14 days of study enrollment and must be Non-lactating patients. Sign written informed consent before conducting any research-related procedures.

You may not qualify if:

• People who are known to be allergic to zl-2306 (niraparib)，brivanib and toripalimab or to active or inactive ingredients of drugs with similar chemical structures to zl-2306 (niraparib），brivanib and toripalimab.
• Multiple factors affecting oral medication (such as inability to swallow, post-gastrointestinal resection, chronic diarrhea, etc.).
• Symptomatic, uncontrolled brain metastases or pia meningeal metastases. No imaging scan is required to confirm brain-free metastases; patients with spinal cord compression may still be considered if they have received targeted treatment and have evidence of clinical stability of the disease for at least\> 28 days (controlled central nervous system metastasis must be in the study Have received treatment such as radiation or chemotherapy for at least 1 month; patients must not have new symptoms related to central nervous system lesions or symptoms that indicate disease progression, and patients either take a stable dose of hormones or do not need to take hormones).
• Underwent major surgery within 3 weeks before the study began, or any surgical effects that have not recovered after surgery, or received chemotherapy.
• Received\> 20% bone marrow palliative radiotherapy 1 week before enrollment. 7.Have aggressive cancers other than cervical cancer (except fully treated basal or squamous cell skin cancer within 2 years before enrollment).
• Patient has a previous or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Suffering from a serious or uncontrolled illness, including but not limited to:
• Uncontrollable nausea and vomiting, inability to swallow research drugs, and any gastrointestinal disorders that may interfere with the metabolism of the drug.
• Active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis C, etc.
• Uncontrolled major seizures, unstable spinal cord compression, superior vena cava syndrome, or other mental illnesses that prevent patients from signing informed consent.
• Immunodeficiency (except splenectomy), or other diseases that the investigator believes may expose patients to high-risk toxicity.
• History of bleeding and thrombosis:
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• Any CTCAE Grade 2 bleeding event within 3 months prior to screening, or CTCAE Grade 3 and above bleeding events within 6 months prior to screening.
• History of gastrointestinal bleeding or clear gastrointestinal bleeding tendency within 6 months before screening. Such as: esophageal varices at risk of bleeding, focal lesions of locally active ulcers, or fecal occult blood +.

Sponsors & Collaborators

• Chongqing University Cancer Hospital: lead

Study Sites (1)

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

RECRUITING

Related Publications (8)

• Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7.

  PMID: 27717299 BACKGROUND

• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.

  PMID: 25651787 RESULT

• Chen WQ, Li H, Sun KX, Zheng RS, Zhang SW, Zeng HM, Zou XN, Gu XY, He J. [Report of Cancer Incidence and Mortality in China, 2014]. Zhonghua Zhong Liu Za Zhi. 2018 Jan 23;40(1):5-13. doi: 10.3760/cma.j.issn.0253-3766.2018.01.002. Chinese.

  PMID: 29365411 RESULT

• Eskander RN, Tewari KS. Immunotherapy: an evolving paradigm in the treatment of advanced cervical cancer. Clin Ther. 2015 Jan 1;37(1):20-38. doi: 10.1016/j.clinthera.2014.11.010.

  PMID: 25592089 RESULT

• Kaelin WG Jr. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer. 2005 Sep;5(9):689-98. doi: 10.1038/nrc1691.

  PMID: 16110319 RESULT

• Chu JS, Ge FJ, Zhang B, Wang Y, Silvestris N, Liu LJ, Zhao CH, Lin L, Brunetti AE, Fu YL, Wang J, Paradiso A, Xu JM. Expression and prognostic value of VEGFR-2, PDGFR-beta, and c-Met in advanced hepatocellular carcinoma. J Exp Clin Cancer Res. 2013 Apr 3;32(1):16. doi: 10.1186/1756-9966-32-16.

  PMID: 23552472 RESULT

• Kirstein MM, Lange A, Prenzler A, Manns MP, Kubicka S, Vogel A. Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data. Oncologist. 2014 Nov;19(11):1156-68. doi: 10.1634/theoncologist.2014-0032. Epub 2014 Oct 17.

  PMID: 25326159 RESULT

• Fakhrejahani E, Toi M. Antiangiogenesis therapy for breast cancer: an update and perspectives from clinical trials. Jpn J Clin Oncol. 2014 Mar;44(3):197-207. doi: 10.1093/jjco/hyt201. Epub 2014 Jan 27.

  PMID: 24474817 RESULT

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

brivanib; toripalimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Qi Zhou, Ph.D.

  Chongqing University Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qi Zhou, Ph.D.

CONTACT

13708384529; qizhou9128@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: May 20, 2020
• Study Start: May 8, 2020
• Primary Completion: April 1, 2022
• Study Completion: July 1, 2022
• Last Updated: May 21, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)