Clinical trial NCT03509246: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ovarian Neoplasm Epithelial
High Grade Serous Carcinoma
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2018-04-26
Enrollment: 44
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall response rate
timeFrame: up to 6yr
measure: Partial response rate
timeFrame: up to 6yr
Secondary outcomes:
measure: Complete remission rate
timeFrame: up to 6yr
measure: Progression-free survival
timeFrame: up to 2yr
measure: Overall survival
timeFrame: up to 6yr
measure: Response period
timeFrame: up to 5yr
measure: Quality of life
timeFrame: up to 6yr
measure: Adverse drug reactions
timeFrame: up to 6yr
measure: Genetic susceptibility assessment
timeFrame: up to 6yr
Other outcomes:
Locations:
city: Seongnam Si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyenggi DO
Study officials:
References:
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.
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.
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.
citation: Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166.
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.