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Non-small Cell Lung CancerPhase 1NCT02728492

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

A Phase 1 study testing Quisinostat, Paclitaxel and Carboplatin in people with Non-small Cell Lung Cancer and Epithelial Ovarian Cancer, run by NewVac LLC at 6 sites in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Quisinostat, Paclitaxel and Carboplatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
6 sitesRussia
Study dates
Aug 2013to Jan 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General criteria for the inclusion of patients with non-small cell lung cancer (NSCLC) and ovarian cancer (OC):
  • 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:
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  • Complete blood count: Absolute neutrophil count:
  • Platelets:
  • Haemoglobin: ≥ 1500/mm3 (1.5 x 109 cells/l)
  • 100 000/mm3 (100 x 109 cells/l)
  • 9.0 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.
  • Functional status of the patient according to the ECOG 0 - 2 Special criteria for patients with NSCLC
  • Histologically or cytologically confirmed diagnosis of non-resectable non-small-cell lung cancer
  • The progression of lung cancer after a maximum of one line of systemic anticancer therapy (adjuvant chemotherapy will be considered first-line therapy if the time from the moment of its completion until disease progression was less than 6 months)
  • No history of treatment with Gemcitabine if the patient is planned for inclusion in the group of chemotherapy with Cisplatin and Gemcitabine, or Paclitaxel if the patient is planned for inclusion in the group of Carboplatin and Paclitaxel.
  • Vital capacity of lung by spirometry data is more than 50% of normal at screening
  • Special inclusion criteria for patients with ovarian cancer
  • Histologically confirmed diagnosis of ovarian cancer.
  • Progression after no more than three modes of anticancer drug therapy for ovarian cancer.

Who cannot join

  • Indications for X-ray therapy or chemoradiation therapy at the time of inclusion, regardless of the treated area;
  • 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);
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  • 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
  • Hypotension (systolic blood pressure < 86 mm Hg or bradycardia with a heart rate of < 50 beats per minute (ECG) except when caused by medications (e.g. beta-blockers).
  • Uncontrolled arterial hypertension (systolic arterial pressure > 170 millimeters of mercury or diastolic blood pressure > 105 millimeters of mercury)
  • Pregnancy and lactation
  • Presence of HIV antibodies, Hepatitis В and С antibodies
  • Drug or alcohol abuse at the moment of screening or in the past which according to the opinion of the Investigator makes the patient unsuitable for participation in the study
  • Significant allergic reactions in medical history
  • Participation in other clinical studies or administration of test drugs during 30 days before beginning of the study or persisting side effect of any of the test drugs;
  • Toxic effects of previous treatments or complications after surgical treatments that did not resolve to grades 1 and/or 0 (according to the CTCAE scale).
  • Patient not willing to participate in the study or unable to understand or follow the protocol instructions.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Russia6 sites

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

    Moscow, 115478

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

    Pyatigorsk, 357502

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

    Saint Petersburg, 197022

  • BioEq LLC

    Saint Petersburg, 197342

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

    Saint Petersburg, 197758

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

    Yaroslavl, 150054

Other trials in Russia

About this study

Official title: Open-label Multicenter Multiple Ascending Dose Study to Evaluate Safety, Tolerability and Pharmacokinetics of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Gemcitabine + Cisplatin Chemotherapy (Second Line for Patients With Non-small Cell Lung Cancer) or Paclitaxel + Carboplatin Chemotherapy (Second Line for Patients With Non-small-cell Lung Cancer, Second and Subsequent Lines for Patients With Epithelial Ovarian Cancer)

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.

Read the detailed description

It was proven that Quisinostat increases HDAC1-inhibited E-cadherin expression (at the low concentrations of 30 nM) which increases susceptibility to epidermal growth factor inhibitors in case of non-small-cell lung cancer and stops proliferation of paclitaxel-resistant cells. Thus, 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 and possibly to resensitiztion in case of acquired or primary resistance.

The main objective of the study is to evaluate the safety and tolerability of Quisinostat in multiple ascending doses and establish its maximum tolerated dose (MTD), administered in combination with standard backbone chemotherapy, as follows: Gemcitabine + Cisplatin in patients with non-small-cell lung cancer (second line) and Paclitaxel + Carboplatin in patients with non-small-cell lung cancer (second line) and in patients with ovarian cancer (second and subsequent lines). MTD is defined as maximum dose at which DLT occurs in no more than 1 patient of 6.

Secondary objectives are:

  • Study of pharmacokinetics (PK) of multiple dosing of Quisinostat administered in combination with chemotherapy, as follows: Gemcitabine + Cisplatin in patients with non-small-cell lung cancer (second line) and Paclitaxel + Carboplatin in patients with non-small-cell lung cancer (second line) and in patients with ovarian cancer (second and subsequent lines) Preliminary estimation of possible effect of the drug, added to chemotherapy, on tumor growth.
Being tested
Quisinostat, Paclitaxel, Carboplatin, Gemcitabine, Cisplatin
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Carcinoma, Ovarian Epithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02728492
Study groupRoleWhat they receive
Quisinostat 8 mg & Paclitaxel & CarboplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin
Quisinostat 10 mg & Paclitaxel & CarboplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin
Quisinostat 12 mg & Paclitaxel & CarboplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin
Quisinostat 8 mg & Gemcitabine 1000 mg/m2 & CisplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin
Quisinostat 10 mg & Gemcitabine 1000 mg/m2 & CisplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin
Quisinostat 12 mg & Gemcitabine 1000 mg/m2 & CisplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin
Quisinostat 12 mg & Gemcitabine 1250 mg/m2 & CisplatinExperimentalQuisinostat 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
Receives: Drug: Quisinostat; Drug: Gemcitabine; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 22 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2016 (estimated)
  2. Study startAug 2013
  3. Primary completionDec 2015
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02728492
Sponsor's protocol ID
ONC-13-NSCLC/OVA-7-QUI-1B
Status last verified
May 2016
First submitted
13 Nov 2015
Last updated
3 May 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: Final results will be published

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Quisinostat, Paclitaxel and Carboplatin in people with Non-small Cell Lung Cancer and Epithelial Ovarian Cancer, run by NewVac LLC at 6 sites in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 22 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02728492.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2016; AzTrials last refreshed its copy on 8 Nov 2026.

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