UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000015193 |
|---|---|
| Receipt number | R000017266 |
| Scientific Title | Phase I of Vorinostat-Iressa combined therapy on resistance by BIM polymorphysim in EGFR Mutant Lung Cancer |
| Date of disclosure of the study information | 2014/09/17 |
| Last modified on | 2016/08/22 08:34:16 |
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Basic information
Public title
Phase I of Vorinostat-Iressa combined therapy on resistance by BIM polymorphysim in EGFR Mutant Lung Cancer
Acronym
VICTORY-J(Vorinostat-Iressa Combined Therapy on Resistance by BIM Polymorphysim in EGFR Mutant Lung Cancer-JAPAN)
Scientific Title
Phase I of Vorinostat-Iressa combined therapy on resistance by BIM polymorphysim in EGFR Mutant Lung Cancer
Scientific Title:Acronym
VICTORY-J(Vorinostat-Iressa Combined Therapy on Resistance by BIM Polymorphysim in EGFR Mutant Lung Cancer-JAPAN)
Region
| Japan |
Condition
Condition
Non-small-cell lung cancer
Classification by specialty
| Pneumology | Hematology and clinical oncology | Adult |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
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.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Others
Developmental phase
Phase I
Assessment
Primary outcomes
MTD (Maximum Tolerated Dose) defined as the highest dose level at which 2 of 6 patients experienced a DLT.
Key secondary outcomes
1)Safety (adverse events generated in from therapy start to the end of dosage end 30th of vorinostat
2)Blood concetnration after administration of vorinostat and gefitinib
3)progression free survival (PFS) period
4)Overall survival (OS) rate
5)Response rate (PR)
6)A response period and complete response period
7)Disease control rate (DCR)
8)Pharmacodynamic effect
Base
Study type
Interventional
Study design
Basic design
Single arm
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
1
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
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.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
1)Histologically or cytologically diagnosed NSCLC (excluding squamous cell carcinoma)
3)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
4)Having a history of treatment with an EGFR-TKI (gefitinib or erlotinib) and a history of pathology deterioration during treatment
6)Confirmed BIM polymorphism by the PCR fragment analytical method and the sequence method at the central laboratory
7)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
8)Ages 20 years and older
9)Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 at the time of consent acquisition
Key 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.
Suffering from a severe or poorly controlled systemic disease (e.g., unstable or decompensated respiratory disease, heart disease, renal disease, and liver disease)
Target sample size
18
Research contact person
Name of lead principal investigator
| 1st name | |
| Middle name | |
| Last name | Seiji Yano |
Organization
Medical Oncology Cancer Research Institute, Kanazawa University
Division name
Medical Oncology
Zip code
Address
13-1 Takara-machi, Kanazawa, Ishikawa 920-0934
TEL
076-265-2780
syano@staff.kanazawa-u.ac.jp
Public contact
Name of contact person
| 1st name | |
| Middle name | |
| Last name | Shinji Takeuchi |
Organization
Cancer Research Center, Kanazawa UNIversity
Division name
Medical Oncology
Zip code
Address
13-1 Takara-machi, Kanazawa, Ishikawa 920-0934
TEL
076-265-2794
Homepage URL
takeuchi@staff.kanazawa-u.ac.jp
Sponsor or person
Institute
Cancer Research Center, Kanazawa University
Institute
Department
Personal name
Funding Source
Organization
Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization
Japanese Governmental office
Nationality of Funding Organization
Japan
Other related organizations
Co-sponsor
Nagoya University Hospital
Tohoku University Hospital
Shizuoka Cancer Center
Institute of Biomedical Research and Innovation Hospital
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Address
Tel
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
金沢大学病院（石川県）、東北大学病院（宮城県）、名古屋大学医学部附属病院（愛知県）、静岡県立静岡がんセンター、先端医療センター（兵庫県）
Other administrative information
Date of disclosure of the study information
| 2014 | Year | 09 | Month | 17 | Day |
Related information
URL releasing protocol
https://clinicaltrials.gov/ct2/show/record/NCT02151721?term=NCT02151721&rank=1
Publication of results
Unpublished
Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Enrolling by invitation
Date of protocol fixation
| 2013 | Year | 06 | Month | 22 | Day |
Date of IRB
Anticipated trial start date
| 2014 | Year | 05 | Month | 30 | Day |
Last follow-up date
| 2016 | Year | 04 | Month | 30 | Day |
Date of closure to data entry
| 2016 | Year | 05 | Month | 30 | Day |
Date trial data considered complete
| 2016 | Year | 06 | Month | 30 | Day |
Date analysis concluded
| 2016 | Year | 09 | Month | 30 | Day |
Other
Other related information
Management information
Registered date
| 2014 | Year | 09 | Month | 17 | Day |
Last modified on
| 2016 | Year | 08 | Month | 22 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017266
