Safety and Efficacy of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Chemotherapy
|ClinicalTrials.gov Identifier: NCT02948075|
Recruitment Status : Completed
First Posted : October 28, 2016
Last Update Posted : June 27, 2018
This is a multicenter, open-label study of safety and efficacy of Quisinostat in combination with Paclitaxel + Carboplatin chemotherapy in patients with metastatic or locally advanced epithelial ovarian cancer, primarily peritoneal or fallopian tube carcinoma, resistant to first line platinum and Paclitaxel based chemotherapy.
The study will be carried out in 5-8 Russian and Belarusian sites. A maximum of 32 patients with metastatic or locally advanced epithelial ovarian cancer, primarily peritoneal or fallopian tube carcinoma, resistant to first line platinum and Paclitaxel based chemotherapy, will be enrolled in the study.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer||Drug: Quisinostat Drug: Paclitaxel Drug: Carboplatin||Phase 2|
The study will be consisted of screening period of 3 weeks before the beginning of Quisinostat administration, followed by the Investigational product treatment period of approximately 18 weeks (up to 6 cycles and 21 days for each cycle), a safety follow-up of 4 weeks after the last administration of the study therapy and post-treatment follow-up aimed at determination of progression-free survival, time to disease progression and overall survival rate in the study population.
An interim analysis will be performed after 10 patients are evaluated for efficacy. If 1 or less from 10 patients have an objective response (OR), the study will be stopped early for futility.
After screening and confirmation of inclusion/exclusion criteria, patients will be asked to come to the site to start taking Quisinostat.
All patients will receive Quisinostat in the dose of 12 mg on Day 1, 3, 5, 7, 9 and 11 of each treatment cycle. Administration of Paclitaxel and Carboplatin will be performed on Day 7 of each cycle. The cycles will be repeated once every 3 weeks (21 days).
In case of severe carboplatin hypersensitivity reaction, it is permitted to switch to Cisplatin (75mg/m2) as alternative to Carboplatin in the subsequent cycles.
Patients will receive up to 6 cycles of study therapy and then patients will continue to be followed-up for ORR, PFS, TTP, OS assessment in the study population.
The Post-treatment follow up will include:
- End of treatment visit will take place in case of treatment's completion within 6 cycles of study therapy.
- Early discontinuation visit will take place in case of the early study termination (before completion of 6 cycles) . The patients will be asked to make an Early discontinuation visit not later than in 4 weeks after administration of the last Investigational product dose.
After End of treatment or Early Discontinuation visit the patient will continue to be followed- for up to 1 year from the start of study treatment or until ICRR-determined progression (or death) (whichever is earlier). This will include tumor assessments every 6 weeks (±7 days).
Following disease progression, the Investigator will contact the patients or their relatives not less than once in 3 months in order to collect information concerning the patient's survival status and, cause of death. This will occur up to 1 year after initial start of treatment on this protocol.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter, Open-label Study of Safety and Efficacy of Quisinostat in Combination With Paclitaxel + Carboplatin Chemotherapy in Patients With Metastatic or Locally Advanced Epithelial Ovarian Cancer, Primarily Peritoneal or Fallopian Tube Carcinoma, Resistant to First Line Platinum and Paclitaxel Based Chemotherapy|
|Study Start Date :||September 2015|
|Actual Primary Completion Date :||December 2016|
|Actual Study Completion Date :||June 16, 2017|
Experimental: Quisinostat 12 mg & Paclitaxel & Carboplatin
One 3-weeks course includes 6 doses of Quisinostat 12 mg at Days 1, 3, 5, 7, 9 and 11 and Paclitaxel 175 mg/m2 and Carboplatin (mg/ml x min) x [GFR (ml/min) + 25] on Day 7 up to 6 cycles.
Other Name: JNJ-26481585
- Objective response rate [ Time Frame: up to week 54 ]assessment of the objective response rate ORR (complete response (CR) plus partial response (PR)) according to RECIST 1.1 criteria
- Progression-free survival (PFS) [ Time Frame: up to week 54 ]
- Time to progression (TTP) [ Time Frame: up to week 54 ]
- Overall survival (OS) [ Time Frame: up to week 54 ]
- The percentage of patients in which the TTP1 on the first line chemotherapy with Carboplatin and Paclitaxel is shorter than TTP2 for the patients on second line chemotherapy with Carboplatin, Paclitaxel and Quisinostat [ Time Frame: up to week 54 ]
- Determination of E-Cadherin, ERCC1 and BRCA1 expression as potential predictive biomarkers for Quisinostat induced sensitivity to chemotherapy [ Time Frame: up to week 54 ]the measurement will be conducted using tumor tissue samples
- Incidence and severity of adverse events (AEs), including serious AEs (SAEs), graded according to the National Cancer Institute (NCI) CTCAE version 4.03 [ Time Frame: up to week 54 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02948075
|Federal State budget Scientific Agency "Russian Oncological Research Center n.a. N.N. Blokhin"|
|Moscow, Russian Federation, 115478|
|Medical Radiological Scientific Center n.a. A.F. Tsyb - branch of Federal State Budget Agency "Public Medical Scientific Radiology Center" of Ministry of Health of Russian Federation|
|Obninsk, Russian Federation, 249036|
|State Budget Agency of Stavropol Territory Healthcare Pyatigorsk Oncologic Dispensary|
|Pyatigorsk, Russian Federation, 357502|
|State Budget Agency of Healthcare "Leningradsky Regional Oncologic Dispensary"|
|St. Petersburg, Russian Federation, 191014|
|State Budget Healthcare Agency "St-Petersburg clinical scientific-practical center of specialized types of medical care (oncology)"|
|St. Petersburg, Russian Federation, 197758|
|St-Petersburg State Budget Agency of Healthcare "Municipal Clinical Oncological Dispensary"|
|St. Petersburg, Russian Federation|
|Principal Investigator:||Sergei A. Tjulandin, Prof.||Russian Oncological Research Center n.a. N.N. Blokhin RAMS|