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

NCT02728492 | Completed Phase 1 DMC

• 1 other identifier: ONC-13-NSCLC/OVA-7-QUI-1B
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

Quisinostat besides its own efficacy, which can potentially lead to better results of polychemotherapy and increase the mean time to progression, it may be demonstrated that Quisinostat leads to sustained tumor sensitivity to platinum drugs. In this study safety and tolerability of multiple administrations of Quisinostat in doses ranging from 8 mg to 12 mg combined with standard backbone chemotherapy in patients with non-small cell lung cancer (second line) and ovarian cancer (second and subsequent lines) will be investigated.

Conditions

Non-small Cell Lung Cancer; Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• safety and tolerability of Quisinostat based on number of patients with treatment -related AEs assessed by CTCAE v4.0, number of patients with abnormal laboratory values and instrumental tests (ECG) that are related to treatment

  22 weeks

Other Outcomes (2)

• Peak Plasma Concentration (Cmax) of Quisinostat

  Day 1, Day 7

• Area under the Quisinostat plasma concentration versus time curve (AUC)

  Day 1, Day 7

Study Arms (7)

Quisinostat 8 mg & Paclitaxel & Carboplatin

EXPERIMENTAL

Quisinostat 8 mg capsule every other day and Paclitaxel 175 mg/m2 on Day 7 of every 3-weeks course and Carboplatin (mg/ml х min) х \[GFR (ml/min) + 25\] on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin

Quisinostat 10 mg & Paclitaxel & Carboplatin

EXPERIMENTAL

Quisinostat 10 mg capsule every other day and Paclitaxel 175 mg/m2 on Day 7 of every 3-weeks course and Carboplatin (mg/ml х min) х \[GFR (ml/min) + 25\] on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin

Quisinostat 12 mg & Paclitaxel & Carboplatin

EXPERIMENTAL

Quisinostat 12 mg capsule every other day and Paclitaxel 175 mg/m2 on Day 7 of every 3-weeks course and Carboplatin (mg/ml х min) х \[GFR (ml/min) + 25\] on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin

Quisinostat 8 mg & Gemcitabine 1000 mg/m2 & Cisplatin

EXPERIMENTAL

Quisinostat 8 mg capsule every other day and Gemcitabine 1000 mg/m2 on Day 7 and on Day 14 of every 3-weeks course and Cisplatin 75 mg/m2 on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin

Quisinostat 10 mg & Gemcitabine 1000 mg/m2 & Cisplatin

EXPERIMENTAL

Quisinostat 10 mg capsule every other day and Gemcitabine 1000 mg/m2 on Day 7 and on Day 14 of every 3-weeks course and Cisplatin 75 mg/m2 on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin

Quisinostat 12 mg & Gemcitabine 1000 mg/m2 & Cisplatin

EXPERIMENTAL

Quisinostat 12 mg capsule every other day and Gemcitabine 1000 mg/m2 on Day 7 and on Day 14 of every 3-weeks course and Cisplatin 75 mg/m2 on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin

Quisinostat 12 mg & Gemcitabine 1250 mg/m2 & Cisplatin

EXPERIMENTAL

Quisinostat 12 mg capsule every other day and Gemcitabine 1250 mg/m2 on Day 7 and on Day 14 of every 3-weeks course and Cisplatin 75 mg/m2 on Day 7 of every 3-weeks course up to 6 cycles

Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Quisinostat DRUG

Also known as: JNJ-26481585

Quisinostat 10 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 10 mg & Paclitaxel & Carboplatin; Quisinostat 12 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 12 mg & Gemcitabine 1250 mg/m2 & Cisplatin; Quisinostat 12 mg & Paclitaxel & Carboplatin; Quisinostat 8 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 8 mg & Paclitaxel & Carboplatin

Paclitaxel DRUG

Quisinostat 10 mg & Paclitaxel & Carboplatin; Quisinostat 12 mg & Paclitaxel & Carboplatin; Quisinostat 8 mg & Paclitaxel & Carboplatin

Carboplatin DRUG

Quisinostat 10 mg & Paclitaxel & Carboplatin; Quisinostat 12 mg & Paclitaxel & Carboplatin; Quisinostat 8 mg & Paclitaxel & Carboplatin

Gemcitabine DRUG

Quisinostat 10 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 12 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 12 mg & Gemcitabine 1250 mg/m2 & Cisplatin; Quisinostat 8 mg & Gemcitabine 1000 mg/m2 & Cisplatin

Cisplatin DRUG

Quisinostat 10 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 12 mg & Gemcitabine 1000 mg/m2 & Cisplatin; Quisinostat 12 mg & Gemcitabine 1250 mg/m2 & Cisplatin; Quisinostat 8 mg & Gemcitabine 1000 mg/m2 & Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• 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
• Age 18 and older
• The value of left ventricular ejection fraction, as determined by echocardiography data, more than 50%
• Patient's ability to carry out visits and study procedures and to comply with the protocol
• Requirements to laboratory parameters determined below:
• Complete blood count: Absolute neutrophil count:
• Platelets:
• Haemoglobin: ≥ 1500/mm3 (1.5 x 109 cells/l)
• /mm3 (100 x 109 cells/l)
• g/dl
• Liver function: Total bilirubin:
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 1.5-fold of the upper limit of normal (ULN)
• ≤ 2.5--fold of ULN or ≤ 5.0-fold of ULN in case of metastases in liver Kidney function: GRF (by Cockcroft-Gault equation) \> 50 ml/min
• The expected survival time not less than 6 months
• Women and men of childbearing potential (not sterile or in menopause less than 2 years) must be practicing an effective method of birth control starting from the screening period, during the study and 6 months after the last administration of the investigational product. Effective methods include use a condom or diaphragm (barrier method) with spermicide.

You may not qualify if:

• Presence of clinical and/or radiological signs of metastases in the brain and meningeal structures (CNS);
• Previous therapy with HDAC inhibitors
• Any contraindications to the chemotherapy with Gemcitabine + Cisplatin or Paclitaxel + Carboplatin (in patients with lung cancer); contraindications to chemotherapy according to the standard chemotherapy combination scheme Paclitaxel + Carboplatin (in female patients with ovarian cancer);
• Any contraindications to administration of glucocorticosteroids, antihistamine drugs, serotonin 5-HT3 receptor antagonists, aprepitant;
• Any contraindications to forced rehydration and/or administration of forced diuresis (in case of lung cancer);
• Conditions that require continuous use of oral anticoagulants, or clinically significant changes in blood coagulation parameters at screening (INR \> 1.5, aPTT\> 1.5 х ULN)
• Conditions that require admission of prohibited drugs, or impossibility to replace those with allowed drugs in the study
• Current infection or other systemic conditions constituting a contraindication to the intended chemotherapy;
• Diseases of the digestive system which may infringe absorption of the investigational product (Crohn's disease, nonspecific ulcerative colitis, irritable bowel syndrome)
• 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 \> 450 ms in men or 470 ms in women (ECG) (calculated according to Fredericia formula), or a diagnosis of long QT syndrome

Sponsors & Collaborators

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

Study Sites (6)

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

Moscow, 115478, Russia

Location

State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk oncology dispensary"

Pyatigorsk, 357502, Russia

Location

Saint-Peterburg State Budgetary healthcare Institution "City Clinical Oncology Dispensary"

Saint Petersburg, 197022, Russia

Location

BioEq LLC

Saint Petersburg, 197342, Russia

Location

State Budget Institution of healthcare "Saint-Petersburg clinical research and practical centre of specialized medical aid (oncology)"

Saint Petersburg, 197758, Russia

Location

State Healthcare Institution of Yaroslavl region "Regional Clinical oncology hospital"

Yaroslavl, 150054, Russia

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Ovarian Epithelial

Interventions

quisinostat; Paclitaxel; Carboplatin; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland 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; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Sergey Tjulandin, Prof

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2015
• First Posted: April 5, 2016
• Study Start: August 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: May 3, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (6)