Safety and Efficacy of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Chemotherapy

NCT02948075 | Completed Phase 2 DMC

• 1 other identifier: ONC-14-OvaII-1-QUI-2
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  assessment of the objective response rate ORR (complete response (CR) plus partial response (PR)) according to RECIST 1.1 criteria

  up to week 54

Secondary Outcomes (6)

• Progression-free survival (PFS)

  up to week 54

• Time to progression (TTP)

  up to week 54

• Overall survival (OS)

  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

  up to week 54

• Determination of E-Cadherin, ERCC1 and BRCA1 expression as potential predictive biomarkers for Quisinostat induced sensitivity to chemotherapy

  up to week 54

Study Arms (1)

Quisinostat 12 mg & Paclitaxel & Carboplatin

EXPERIMENTAL

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.

Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Quisinostat DRUG

Also known as: JNJ-26481585

Quisinostat 12 mg & Paclitaxel & Carboplatin

Paclitaxel DRUG

Quisinostat 12 mg & Paclitaxel & Carboplatin

Carboplatin DRUG

Quisinostat 12 mg & Paclitaxel & Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed patient's information sheet and informed consent form to participate in the study.
• Histological confirmed diagnosis of serous epithelial ovarian, primarily peritoneal or fallopian tube carcinoma.
• Females aged ≥ 18 years.
• Patients must have an ECOG status of 0 or 1.
• Patients must have received only 1 prior line of platinum and Paclitaxel based chemotherapy.
• Tumor progression observed not less than 1 month and no more than 6 months after completion of the planned number of cycles of first line platinum/Paclitaxel based chemotherapy (Carboplatin in the dose AUC5-6 or Cisplatin in the dose ≥ 75 mg/m2, in combination with paclitaxel for 6 q3-4 wk cycles) and indications for undergoing the second line chemotherapy.
• The patients must have at least one measurable lesion according to RECIST 1.1 criteria.
• Tissue block from archived material at diagnosis must be available and be submitted for predictive biomarker analysis.
• Patient's ability to carry out visits and study procedures and to comply with the protocol.
• Requirements for laboratory parameters determined below:
• Hematology: Absolute neutrophil count:
• Platelets:
• Hemoglobin: ≥ 1,500/mm3 (1.5 x 109 cells/L)
• ,000/mm3 (100 x 109 cells/L)
• g/dl Liver function: Total bilirubin: ≤ 1.5x upper limit of normal (ULN)

You may not qualify if:

• Patients previously treated with an HDAC inhibitor. Patients, who have been treated with Valproate for convulsions can be included, however only if the treatment has taken place \> 30 days before the screening.
• Presence of specific toxicities of ≥ I grade, according to the NCI-CTCAE v.4.3, related to any prior anti-cancer therapy (excluding alopecia)
• Patients with subsequent debulking operation (after first line chemotherapy) or radiotherapy due to the disease recurrence.
• Patients who have undergone lower pelvis radiotherapy.
• Patients with active or uncontrolled infection.
• Patients with antibodies to human immunodeficiency virus (HIV), or hepatitis C virus (HCV), active hepatitis B virus (HBsAg).
• History of other malignancies with the exception of basal cell carcinoma of the skin or cervical cancer in situ, that had undergone surgical removal or treatment within ≥ 5 years before the screening.
• Patients with known cerebral metastases or clinical signs of cerebral metastases.
• Have a history of severe hypersensitivity reaction to carboplatin, paclitaxel or agents within the histone deacetylase inhibitor group.
• Clinically significant cardiovascular diseases including:
• Myocardial infarction within 12 months before screening
• Unstable angina within 12 months before screening
• Congestive heart failure Class III or IV according to the New York Heart Association criteria (NYHA)
• Clinically significant ventricular arrhythmia including ventricular tachycardia, ventricular fibrillation, history of cardiac arrest, atrioventricular block (Mobitz II or III), use of cardiostimulator
• QTc interval \> 470 ms (ECG) (calculated according to Fredericia formula), or a diagnosis of long QTc syndrome

Sponsors & Collaborators

• NewVac LLC: lead
• Janssen Pharmaceutica N.V., Belgium: collaborator

Study Sites (6)

Federal State budget Scientific Agency "Russian Oncological Research Center n.a. N.N. Blokhin"

Moscow, 115478, Russia

Location

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, 249036, Russia

Location

State Budget Agency of Stavropol Territory Healthcare Pyatigorsk Oncologic Dispensary

Pyatigorsk, 357502, Russia

Location

State Budget Agency of Healthcare "Leningradsky Regional Oncologic Dispensary"

Saint Petersburg, 191014, Russia

Location

State Budget Healthcare Agency "St-Petersburg clinical scientific-practical center of specialized types of medical care (oncology)"

Saint Petersburg, 197758, Russia

Location

St-Petersburg State Budget Agency of Healthcare "Municipal Clinical Oncological Dispensary"

Saint Petersburg, Russia

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

quisinostat; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Sergei A. Tjulandin, Prof.

  Russian Oncological Research Center n.a. N.N. Blokhin RAMS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2016
• First Posted: October 28, 2016
• Study Start: September 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: June 16, 2017
• Last Updated: June 27, 2018

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (6)