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

Phase 2
Conditions
Ovarian Neoplasm Epithelial
High Grade Serous Carcinoma
Interventions
Drug: Pegylated liposomal doxorubicin plus Bortezomib
Registration Number
NCT03509246
Lead Sponsor
Seoul National University Hospital
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
44
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Pegylated liposomal doxorubicin plus Bortezomib combinationPegylated liposomal doxorubicin plus BortezomibAt BRCA wild-type platinum-resistant recurrent ovarian cancer patients, Pegylated liposomal doxorubicin and Bortezomib combination therapy for six cycles.
Primary Outcome Measures
NameTimeMethod
Overall response rateup to 6yr

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

Partial response rateup to 6yr

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
NameTimeMethod
Complete remission rateup to 6yr

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 survivalup to 2yr

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

Adverse drug reactionsup to 6yr

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 assessmentup to 6yr

Response rate in subjects with CCNE1 amplification.

Overall survivalup to 6yr

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

Response periodup to 5yr

duration of objective response period

Quality of lifeup to 6yr

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

Trial Locations

Locations (1)

Seoul National University Bundang Hospital

🇰🇷

Seongnam Si, Gyenggi DO, Korea, Republic of

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