Back to results

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

Primary Purpose

Ovarian Neoplasm Epithelial, High Grade Serous Carcinoma

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Pegylated liposomal doxorubicin plus Bortezomib

About this trial

This is an interventional treatment trial for Ovarian Neoplasm Epithelial

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Seoul National University Bundang HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pegylated liposomal doxorubicin plus Bortezomib combination

Arm Description

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

Outcomes

Primary Outcome Measures

Overall response rate

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

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.

Secondary Outcome Measures

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

Progression-free survival

Patients who have recurred disease after the end of the administration are identified and measured.

Overall survival

Patients who died from illness after the start of treatment were identified and measured.

Response period

duration of objective response period

Quality of life

Evaluation via Physicians Global Assessment to measure the quality of life and pain descriptive diary.

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.

Genetic susceptibility assessment

Response rate in subjects with CCNE1 amplification.

Full Information

NCT ID

NCT03509246

First Posted

March 29, 2018

Last Updated

January 12, 2020

Sponsor

Seoul National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03509246

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Unknown status

Study Start Date

May 15, 2018 (Actual)

Primary Completion Date

March 2022 (Anticipated)

Study Completion Date

March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Seoul National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Neoplasm Epithelial, High Grade Serous Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pegylated liposomal doxorubicin plus Bortezomib combination

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Pegylated liposomal doxorubicin plus Bortezomib

Intervention Description

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

Primary Outcome Measure Information:

Title

Overall response rate

Description

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

Time Frame

up to 6yr

Title

Partial response rate

Description

Time Frame

up to 6yr

Secondary Outcome Measure Information:

Title

Complete remission rate

Description

The proportion of subjects who had a confirmed complete response according to RECIST criteria version 1.1 in the modified ITT analysis group

Time Frame

up to 6yr

Title

Progression-free survival

Description

Patients who have recurred disease after the end of the administration are identified and measured.

Time Frame

up to 2yr

Title

Overall survival

Description

Patients who died from illness after the start of treatment were identified and measured.

Time Frame

up to 6yr

Title

Response period

Description

duration of objective response period

Time Frame

up to 5yr

Title

Quality of life

Description

Evaluation via Physicians Global Assessment to measure the quality of life and pain descriptive diary.

Time Frame

up to 6yr

Title

Adverse drug reactions

Description

Time Frame

up to 6yr

Title

Genetic susceptibility assessment

Description

Response rate in subjects with CCNE1 amplification.

Time Frame

up to 6yr

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kidong Kim

Phone

82-31-787-7262

kidong.kim.md@gmail.com

Facility Information:

Facility Name

Seoul National University Bundang Hospital

City

Seongnam Si

State/Province

Gyenggi DO

ZIP/Postal Code

463707

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

KIDONG KIM, MD

Phone

82-31-787-7262

KIDONG.KIM.MD@GMAIL.COM

First Name & Middle Initial & Last Name & Degree

KIDONG KIM, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

17679727

Citation

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.

Results Reference

background

PubMed Identifier

24218601

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.

Results Reference

background

PubMed Identifier

26187614

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.

Results Reference

background

PubMed Identifier

21720365

Citation

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.

Results Reference

background

PubMed Identifier

35738633

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs