Bortezomib and Pegylated Liposomal Doxorubicin in BRCA Wild-type Platinum-resistant Recurrent Ovarian Cancer Patients

NCT03509246 | Unknown Phase 2 FDA Drug

• 1 other identifier: EBLIN
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase II clinical trial to evaluate the safety and efficacy of Bortezomib plus Pegylated liposomal doxorubicin combination therapy in a histologic type of high-grade serous carcinoma without BRCA mutation among patients with platinum-resistant recurrent ovarian cancer.

Conditions

Ovarian Neoplasm Epithelial; High Grade Serous Carcinoma

Outcome Measures

Primary Outcomes (2)

• Overall response rate

  In the modified ITT group, the response rate to combination therapy with bortezomib and PLD 2

  up to 6yr

• Partial response rate

  The percentage of patients who received a confirmed treatment response over a partial response according to the RECIST criteria version 1.1 in the modified ITT analysis group. The evaluation is based on the researchers of each participating organization.

  up to 6yr

Secondary Outcomes (7)

• Complete remission rate

  up to 6yr

• Progression-free survival

  up to 2yr

• Overall survival

  up to 6yr

• Response period

  up to 5yr

• Quality of life

  up to 6yr

Study Arms (1)

Pegylated liposomal doxorubicin plus Bortezomib combination

EXPERIMENTAL

At BRCA wild-type platinum-resistant recurrent ovarian cancer patients, Pegylated liposomal doxorubicin and Bortezomib combination therapy for six cycles.

Drug: Pegylated liposomal doxorubicin plus Bortezomib

Interventions

Pegylated liposomal doxorubicin plus Bortezomib DRUG

Pegylated liposomal doxorubicin 40mg/m2 subcutaneous for 60 - 90 minutes at day 4 plus Bortezomib 1.3mg/m2 subcutaneous injection at day 1,4,8,11 for 6 cycles

Pegylated liposomal doxorubicin plus Bortezomib combination

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer based on histologic findings obtained from biopsy/surgery and having a histologic type of high-grade serous cancer.
• In the absence of a mutation of the BRCA gene (no germline mutation should be identified, not in the case of a somatic mutation)
• Recurrence within 6 months after platinum-based chemotherapy.
• ECOG performance 2 points or less.
• Blood tests performed within 2 weeks of enrollment meet the following results: Neutrophil \> 1,500/mm3; Platelet \> 100,000/mm3; Hemoglobin \> 9.0 g/dL; Total bilirubin \< 1.5 x upper limit of normal (ULN); AST/ALT \< 3.0 x ULN (or \< 5 x ULM in case of liver metastases); Creatinine \< 1.5 x ULN; Electrolytes should be within normal limits.
• Patients who understand the content of the study description and voluntarily agree in writing.
• Patients who are willing and able to adhere to the visit schedule, treatment plan, laboratory tests, and other testing procedures.

You may not qualify if:

• Patients previously treated with three or more anticancer regimens. Maintenance therapy is not considered a separate regimen (eg\> paclitaxel-carboplatin-bevacizumab therapy). In the combined chemotherapy, when one drug is subtracted due to toxicity, the regimen is not counted as a change (Eg\> paclitaxel-carboplatin chemotherapy, paclitaxel was discontinued due to neurotoxicity and carboplatin alone was not considered as a change of regimen).
• Previous refractory to ovarian cancer chemotherapy.
• Patients diagnosed with other tumors other than ovarian cancer for the last 5 years (not CIS).
• pregnant woman.
• Patients with uncontrolled infection.
• In the case of congenital immune disease or acquired immune deficiency syndrome.
• Women in lactation.
• History with Grade 3 or higher peripheral neuropathy.
• History of hypersensitivity reactions to PLD or bortezomib.
• If the physician is judged to have any serious illness or medical condition for which the patient is not suitable for the study.
• Patients with confirmed BRCA somatic mutations.
• Patients with acute diffuse infiltrative lung disease and cardiovascular disease.

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, Gyenggi DO, 463707, South Korea

RECRUITING

Related Publications (5)

• Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. doi: 10.1200/JCO.2006.10.5460. Epub 2007 Aug 6.

  PMID: 17679727 BACKGROUND

• Etemadmoghadam D, Weir BA, Au-Yeung G, Alsop K, Mitchell G, George J; Australian Ovarian Cancer Study Group; Davis S, D'Andrea AD, Simpson K, Hahn WC, Bowtell DD. Synthetic lethality between CCNE1 amplification and loss of BRCA1. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19489-94. doi: 10.1073/pnas.1314302110. Epub 2013 Nov 11.

  PMID: 24218601 BACKGROUND

• Kim G, Ison G, McKee AE, Zhang H, Tang S, Gwise T, Sridhara R, Lee E, Tzou A, Philip R, Chiu HJ, Ricks TK, Palmby T, Russell AM, Ladouceur G, Pfuma E, Li H, Zhao L, Liu Q, Venugopal R, Ibrahim A, Pazdur R. FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Clin Cancer Res. 2015 Oct 1;21(19):4257-61. doi: 10.1158/1078-0432.CCR-15-0887. Epub 2015 Jul 17.

  PMID: 26187614 BACKGROUND

• Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166.

  PMID: 21720365 BACKGROUND

• Lee YJ, Seol A, Lee M, Kim JW, Kim HS, Kim K, Suh DH, Kim S, Kim SW, Lee JY. A Phase II Trial to Evaluate the Efficacy of Bortezomib and Liposomal Doxorubicin in Patients With BRCA Wild-type Platinum-resistant Recurrent Ovarian Cancer (KGOG 3044/EBLIN). In Vivo. 2022 Jul-Aug;36(4):1949-1958. doi: 10.21873/invivo.12917.

  PMID: 35738633 DERIVED

MeSH Terms

Interventions

liposomal doxorubicin; Bortezomib

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Kidong Kim

CONTACT

82-31-787-7262; kidong.kim.md@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 26, 2018
• Study Start: May 15, 2018
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: January 14, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)