- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02151721
Phase I of Vorinostat-Iressa Combined Therapy on Resistance by BIM Polymorphysim in EGFR Mutant Lung Cancer (VICTORY-J)
February 1, 2018 updated by: Seiji Yano, M.D., Ph.D., Kanazawa University
- Gefitinib is an orally active epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). However, 20-30% of patients with EGFR-activating mutations show intrinsic resistance to EGFR-TKI.
- EGFR-mutant non-small cell lung cancer (NSCLC) cells with BIM (BCL2L11) deletion polymorphism show the impaired generation of BIM with the proapoptotic BH3 domain, as well as resistance to EGFR-TKI-induced apoptosis.
- Both BIM polymorphism (12.9%) and EGFR mutations (50% in lung adenocarcinoma) are more prevalent in the East Asian than in Caucasian populations. BIM is a BH3-only proapoptotic member of the Bcl-2 protein family. BIM upregulation is required for apoptosis induction by EGFR-TKI in EGFR-mutant NSCLC.
- Vorinostat (suberoylanilide hydroxamic acid [SAHA]) is a small-molecule inhibitor of histone deacetylase (HDAC) and induces cell differentiation, cell cycle arrest, and apoptosis in several tumor cells. HDAC inhibition can epigenetically restore BIM function and death sensitivity of EGFR-TKI in patients with EGFR-mutant NSCLC in whom resistance to EGFR-TKI is associated with a common BIM polymorphism. EGFR-TKI resistance due to the BIM polymorphism may be able to be circumvented in combination with HDAC inhibition of vorinostat with gefitinib in NSCLC.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
Detailed Description
- A cohort of three patients will be treated at each dose level for one cycle (28 days per cycle).
- Treatment will be continued if no DLTs are recorded, and three patients will be treated at the next higher dose level.
- If a patient of the cohort develops a DLT, however, another cohort of three patients will be treated for 1 cycle.
- If more DLTs do not develop, dose escalation continues.
- If more than one of three patients develop a DLT at any dose level, another cohort of three patients will be treated at the next lower dose level.
- If no DLTs are recorded in any of the cohorts, the number of patients per cohort will be increased from 3 to 6.
- Up to 12 patients will be enrolled at the MTD.
- Therefore, the phase II dose for this combined therapy will be defined as the highest dose level at which six patients were treated and less than three DLTs developed.
Study Type
Interventional
Enrollment (Actual)
12
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Aichi
-
Nagoya, Aichi, Japan, 466-8560
- Nagoya University Graduate School of Medicine
-
-
Hyogo-ken
-
Kobe, Hyogo-ken, Japan, 650-0047
- Institute of Biomedical Research and Innovation Hospital
-
-
Ishikawa
-
Kanazawa, Ishikawa, Japan, 920-0934
- Kanazawa University Hospital
-
-
Miyagi
-
Sendai, Miyagi, Japan, 980-8574
- Tohoku University Hospital
-
-
Shizuoka
-
Sunto-gun, Shizuoka, Japan, 411-8777
- Shizuoka Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically or cytologically diagnosed NSCLC (excluding squamous cell carcinoma)
- NSCLC of clinicopathologic stage IIIB or IV for which radical radiation therapy is impracticable, or recurrence after surgery
- EGFR mutations (deletion of exon 19 and L858R mutation of exon 21) for which the clinical benefits of an EGFR-TKI (gefitinib or erlotinib) are recognized by testing methods that are listed by the national health insurance
- Having a history of treatment with an EGFR-TKI (gefitinib or erlotinib) and a history of pathology deterioration during treatment
- Having a history of treatment with cytotoxic anticancer agents (not including pre- or postoperative chemotherapy that has passed 1 or more year from the day of final administration)
- Confirmed BIM polymorphism by the PCR fragment analytical method and the sequence method at the central laboratory
- Having a lesion measureable according to the RECIST guidelines revised version 1.1 (20 mm or larger in 10-mm slice CT, 10 mm or larger in 5-mm slice CT, 15 mm or larger in the minor axis of a lymph node). Confirmed advance of the pathology at the site of irradiation after irradiation in a patient who only has an irradiated lesion
- Ages 20 years and older
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 at the time of consent acquisition
- Having adequate bone marrow (neutrophil count: 1,500/L, Platelet count: 100,000/L), hepatic (total bilirubin level: 1.5-fold or less of the upper limit of reference value at each institution), renal (creatinine level: 1.5 mg/dL), and respiratory functions (PaO2: 70 torr or SpO2: 94%) within 14 days before entry.
- An estimated life expectancy of 12 or more weeks after the onset of protocol treatment
- A patient whose acute toxicities of prior treatments have recovered to the baseline level in the most recent prior treatment, excepting adverse events considered not to be of safety concern at the discretion of the investigator (subinvestigator)
- A patient negative for the urinary pregnancy test to be performed at the time of screening prior to the onset of protocol treatment
- Acquisition of written informed consent to participate in the present study from the patient after receiving a satisfactory explanation about study details
Exclusion Criteria:
- Within 4 weeks after the final administration of a cytotoxic anticancer agent. Allowable enrollment when a 7-day washout is completed after the final administration of an EGFR-TKI. Surgery of a primary tumor or to the mediastinum must be completed at least 6 months before the onset of protocol treatment.
- Radiotherapy to the lungs considered necessary at the time of study entry or in the near future.
- Having an interstitial lung disease (including acute pulmonary disorder, interstitial pneumonia, and drug inducibility) or having a history thereof.
- Having radiation pneumonitis or having a history thereof.
- Having a large volume of or uncontrollable pleural effusion, ascites, or pericardial effusion
- Detection of known EGFR-TKI resistance acquired by mutations of the genes, e.g., T790M.
- Having a serious infection and other serious complications (e.g., gastrointestinal bleeding).
- Suffering from a severe or poorly controlled systemic disease (e.g., unstable or decompensated respiratory disease, heart disease, renal disease, and liver disease)
- Having an active, as well as poorly controlled or symptomatic metastasis to the central nervous system (involving cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, or invasion due to disease progress). Even with a history of metastasis to the central nervous system or of spinal compression.
- Having an active double cancer.
- Verified HBs antigen positivity or HCV antibody positivity (excluding the case of confirmed HCV-RNA negativity)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: vorinostat, gefitinib, combination
single arm vorinostat plus gefitinib
|
Vorinostat 200, 300, or 400 mg orally once daily on days 1-7 with washout on days 8-14 plus gefitinib 250 mg orally once daily on days 1-14
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD (Maximum Tolerated Dose)
Time Frame: Second cycle (Day 28)
|
MTD (Maximum Tolerated Dose)defined as the highest dose level at which < 2 out of 6 patients experienced a DLT.
|
Second cycle (Day 28)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Seiji Yano, MD, PhD, Kanazawa University Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
June 1, 2014
Primary Completion (ANTICIPATED)
February 20, 2018
Study Completion (ANTICIPATED)
February 20, 2018
Study Registration Dates
First Submitted
May 28, 2014
First Submitted That Met QC Criteria
May 28, 2014
First Posted (ESTIMATE)
May 30, 2014
Study Record Updates
Last Update Posted (ACTUAL)
February 5, 2018
Last Update Submitted That Met QC Criteria
February 1, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Histone Deacetylase Inhibitors
- Gefitinib
- Vorinostat
Other Study ID Numbers
- H25-S-I-005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
The 12th patient in stage 3 was registered.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Non-Small-Cell Lung Carcinoma
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Bristol-Myers SquibbCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung Carcinoma | Non-Squamous Non-Small...United States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingLung Non-Squamous Non-Small Cell Carcinoma | Stage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage II Lung Non-Small Cell Cancer AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7United States, Puerto Rico
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Recurrent Lung Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IA...United States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingStage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage II Lung Non-Small Cell Cancer AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Stage I Lung Non-Small Cell Cancer AJCC v7 | Stage...United States
-
National Cancer Institute (NCI)Active, not recruitingStage IIIA Lung Non-Small Cell Cancer AJCC v7 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IV Lung Non-Small Cell Cancer AJCC v7 | Stage III Lung Non-Small Cell Cancer AJCC...United States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Society of Thoracic RadiologyActive, not recruitingStage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
Clinical Trials on Vorinostat, gefitinib
-
Sun Yat-sen UniversityUnknown
-
Peter MacCallum Cancer Centre, AustraliaGlaxoSmithKline; Merck Sharp & Dohme LLCTerminatedFollicular Lymphoma | Mantle Cell Lymphoma | Marginal Zone LymphomaAustralia
-
Qilu Pharmaceutical Co., Ltd.UnknownNon-small-cell Lung CancerChina
-
Sun Yat-sen UniversityWu Jieping Medical FoundationCompletedNon-small Cell Lung CancerChina
-
Jiangsu Famous Medical Technology Co., Ltd.UnknownNon-small Cell Lung Cancer
-
Indiana University School of MedicineBayerCompletedMyelodysplastic Syndromes | Leukemia, Myeloid, Acute | Leukemia, Promyelocytic, AcuteUnited States
-
AstraZenecaCompletedNeoplasms, Squamous CellUnited States, Czech Republic, Poland, Germany, Belgium, Taiwan, India, Serbia
-
Armando Santoro, MDTerminatedSmall Cell Lung CancerItaly
-
The Methodist Hospital Research InstituteWithdrawnNon-Hodgkin Lymphoma
-
Merck Sharp & Dohme LLCCompleted