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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ovarian Neoplasm Epithelial, High Grade Serous Carcinoma

Intervention / Treatment
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* Drug: Pegylated liposomal doxorubicin plus Bortezomib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegylated liposomal doxorubicin plus Bortezomib combination<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Progression-free survival | Patients who have recurred disease after the end of the administration are identified and measured. | up to 2yr | 
| Overall survival | Patients who died from illness after the start of treatment were identified and measured. | up to 6yr | 
| Response period | duration of objective response period | up to 5yr | 
| Quality of life | Evaluation via Physicians Global Assessment to measure the quality of life and pain descriptive diary. | up to 6yr | 
| 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 | 
| Genetic susceptibility assessment | Response rate in subjects with CCNE1 amplification. | up to 6yr |