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

High Grade Serous Carcinoma Clinical Trial

Official title:

A Phase II Trial to Evaluate the Efficacy of Bortezomib and Pegylated Liposomal Doxorubicin in Patients With BRCA Wild-type Platinum-resistant Recurrent Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03509246
• Other study ID #: EBLIN
• Status: Recruiting
• Phase: Phase 2
• Start date: May 15, 2018
• Est. completion date: March 2022

Study information

• Verified date: January 2020
• Source: Seoul National University Hospital
• Contact: Kidong Kim
• Phone: 82-31-787-7262
• Email: kidong.kim.md[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Subjects are dosed with Bortezomib and PLD for a maximum of 6 cycles of 4 weeks. The response rate is evaluated with CT according to RECIST criteria ver 1.1. The efficacy and safety of the drug are assessed at the time of recurrence, at the time of death, or after 24 months after the end of the study drug administration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: March 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• High Grade Serous Carcinoma
• Ovarian Neoplasm Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• Pegylated liposomal doxorubicin plus Bortezomib
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

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam Si	Gyenggi DO

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166. Erratum in: Nature. 2012 Oct 11;490(7419):298. — View Citation

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. — View Citation

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. Review. — View Citation

Orlowski RZ, Nagler A, Sonneveld P, Bladé 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. Epub 2007 Aug 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	In the modified ITT group, the response rate to combination therapy with bortezomib and PLD 2	up to 6yr
Primary	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	Complete remission rate	The proportion of subjects who had a confirmed complete response according to RECIST criteria version 1.1 in the modified ITT analysis group	up to 6yr
Secondary	Progression-free survival	Patients who have recurred disease after the end of the administration are identified and measured.	up to 2yr
Secondary	Overall survival	Patients who died from illness after the start of treatment were identified and measured.	up to 6yr
Secondary	Response period	duration of objective response period	up to 5yr
Secondary	Quality of life	Evaluation via Physicians Global Assessment to measure the quality of life and pain descriptive diary.	up to 6yr
Secondary	Adverse drug reactions	To be evaluated according to NCI CTCAE version 4.03 Frequency of occurrence of each drug adverse reaction and 95% confidence interval, grade 3 or higher, the frequency of adverse drug events and 95% confidence interval.	up to 6yr
Secondary	Genetic susceptibility assessment	Response rate in subjects with CCNE1 amplification.	up to 6yr