Ovarian CancerPhase 2NCT02948075
Safety and Efficacy of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Chemotherapy
A Phase 2 study testing Quisinostat, Paclitaxel and Carboplatin in people with Ovarian Cancer, run by NewVac LLC at 6 sites in Russia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Quisinostat, Paclitaxel and Carboplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 6 sitesRussia
- Study dates
- Sep 2015to 16 Jun 2017
- Phase
- Phase 2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
- 100,000/mm3 (100 x 109 cells/L)
- 9.0 g/dl Liver function: Total bilirubin: ≤ 1.5x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT):
- Alkalinephosphatase:
- 2.5x ULN, or ≤ 5.0 x ULN in the case of liver metastasis
- 5.0 x ULN Renal function: Serum creatinine: ≤2 mg/dL Coagulation panel: Activated partial thromboplastin time (aPTT): ≤ 1.5 x ULN
- The expected survival time not less than 6 months.
- Women of childbearing potential (not sterile or in menopause less than 2 years) must be practicing an effective method of birth control during the whole period of the study and 6 months after the last administration of the investigational product. Effective methods include usage of a condom or diaphragm (barrier method) with spermicide.
Who cannot join
- 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.
- Have received treatment for ovarian cancer with any other prior chemotherapy than platinum (Carboplatin (AUC 5-6) or Cisplatin (≥ 75 mg/m2)) and paclitaxel (175-200 mg/m2) q3-4 wk for 6 cycles. Additional first line chemotherapy or prior treatment with additional investigational anticancer therapy is also an exclusion criterion.
- 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.
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- 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.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess during the year prior to inclusion.
- 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
- 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 mm Hg or diastolic blood pressure > 105 mm Hg)
- Pregnancy and lactation
- 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
- Inability to read or write; inability to understand and comply with the procedures of the study protocol; failure to comply with the treatment, which, in opinion of the Investigator, may affect the results of the study or the patient's safety and prevent the patient from further participation in the study; any other associated medical or serious mental conditions that make the patient unsuitable for participation in the clinical study, limit the validity of informed consent or may affect the patient's ability to participate in the study
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Russia6 sites
Federal State budget Scientific Agency "Russian Oncological Research Center n.a. N.N. Blokhin"
Moscow, 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, 249036
State Budget Agency of Stavropol Territory Healthcare Pyatigorsk Oncologic Dispensary
Pyatigorsk, 357502
State Budget Agency of Healthcare "Leningradsky Regional Oncologic Dispensary"
Saint Petersburg, 191014
State Budget Healthcare Agency "St-Petersburg clinical scientific-practical center of specialized types of medical care (oncology)"
Saint Petersburg, 197758
St-Petersburg State Budget Agency of Healthcare "Municipal Clinical Oncological Dispensary"
Saint Petersburg
About this study
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
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.
Read the detailed description
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.
- Conditions
- Ovarian Cancer
- Being tested
- Quisinostat, Paclitaxel, Carboplatin
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuisinostatDrug
Also called JNJ-26481585
PaclitaxelDrug
CarboplatinDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Quisinostat; Drug: Paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
assessment of the objective response rate ORR (complete response (CR) plus partial response (PR)) according to RECIST 1.1 criteria
Measured: up to week 54
Secondary outcomes (6)
Progression-free survival (PFS)
Measured: up to week 54
Time to progression (TTP)
Measured: up to week 54
Overall survival (OS)
Measured: 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
Measured: up to week 54
Determination of E-Cadherin, ERCC1 and BRCA1 expression as potential predictive biomarkers for Quisinostat induced sensitivity to chemotherapy
the measurement will be conducted using tumor tissue samples
Measured: up to week 54
Incidence and severity of adverse events (AEs), including serious AEs (SAEs), graded according to the National Cancer Institute (NCI) CTCAE version 4.03
Measured: up to week 54
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study startSep 2015
- Primary completionDec 2016
- Study completion16 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewVac LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Pharmaceutica N.V., Belgium
- Responsible party
- Sponsor
- Investigators
- Sergei A. Tjulandin, Prof., Principal investigator, Russian Oncological Research Center n.a. N.N. Blokhin RAMS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02948075
- Sponsor's protocol ID
- ONC-14-OvaII-1-QUI-2
- Status last verified
- Dec 2016
- First submitted
- 24 Oct 2016
- Last updated
- 27 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02948075
- Acronym / sponsor ID
- ONC-14-OvaII-1-QUI-2
- Conditions
- Ovarian Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- NewVac LLCIndustry (pharma, biotech, devices)
- Collaborators
- Janssen Pharmaceutica N.V., Belgium
- Study start
- Sep 2015
- Primary completion
- Dec 2016 (actual)
- Study completion
- 16 Jun 2017 (actual)
- First posted
- 28 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Quisinostat 12 mg & Paclitaxel & Carboplatin | Experimental | Drug: Quisinostat, Drug: Paclitaxel, Drug: CarboplatinOne 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
- Have received treatment for ovarian cancer with any other prior chemotherapy than platinum (Carboplatin (AUC 5-6) or Cisplatin (≥ 75 mg/m2)) and paclitaxel (175-200 mg/m2) q3-4 wk for 6 cycles. Additional first line chemotherapy or prior treatment with additional investigational anticancer therapy is also an exclusion criterion.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QuisinostatAlso: JNJ-26481585 | Drug | Quisinostat 12 mg & Paclitaxel & Carboplatin |
| Paclitaxel | Drug | Quisinostat 12 mg & Paclitaxel & Carboplatin |
| Carboplatin | Drug | Quisinostat 12 mg & Paclitaxel & Carboplatin |
Primary outcome
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
6 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sergei A. Tjulandin, Prof. principal investigator
Russian Oncological Research Center n.a. N.N. Blokhin RAMS
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Quisinostat, Paclitaxel and Carboplatin in people with 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 21 inclusion and 22 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 27 Jun 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Objective response rate (time frame: up to week 54). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2018.