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

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

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.

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.

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.