UMIN-CTR Clinical Trial

Basic information
Public title	An Open label Phase I Study to Evaluate the Safety and Efficacy of OBP-301 with Pembrolizumab in Patients with advanced solid tumors.
Acronym	OBP+Pem
Scientific Title	An Open label Phase I Study to Evaluate the Safety and Efficacy of OBP-301 with Pembrolizumab in Patients with advanced solid tumors.
Scientific Title:Acronym	OBP+Pem
Region	Japan

Condition
Condition	solid tumor
Classification by specialty	Gastroenterology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Phase 1a part: To evaluate safety and tolerability of the combination of OBP-301 and Pembrolizumab in patients with advanced or metastatic solid tumor and to determine the recommended dose in phase 1b part. Phase 1b part: To evaluate safety and potential efficacy of the combination of OBP-301 and Pembrolizumab in patients in expanded arm.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Dose limiting toxicity (DLT)
Key secondary outcomes	Response rate by the response criteria in solid tumors (RECIST) ver1.1: RR Progression free survival: PFS Rate of adverse event

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	OBP-301: Intratumoral injection directly into the target region of a tumor at Day 1, Day 15, and Day 29 Dose of OBP-301 in Phase 1a: 1x10^10 (Cohort 1), 1x10^11 (Cohort 2), 1x10^12VP (Cohort 3)(VP:virus particle) Additional administration of OBP-301 After the recommended dose of OBP-301 has been established, additional administration of OBP-301 is allowed. After completion of administration of OBP-301 on Day 1 - Day 29(+/- 4 days), if the target region has not disappeared, additional administration of OBP-301 is allowed after Day 43 or later. The patients in Phase 1a, Pembrolizumab administration has continued, are included. The recommended dose determined in the Phase 1a part will be administered 3 times biweekly (+/- 4 days); max 4 cycles. Pembrolizumab: Administration at a dose of 200 mg/body on Day 8. The administration of Pembrolizumab will be repeated until meeting the discontinuation criteria.
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	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Be willing and able to provide written informed consent/assent for the trial. 2) Be >=18 years of age on the day of signing the informed consent. 3) Have an ECOG performance status of 0 or 1. 4) Have histologically or cytologically confirmed advanced or metastatic solid tumor with possibility of intratumoral injection, for which no effective standard therapy exists or standard therapy has failed. 5) Have one or more evaluable lesions based on RECIST 1.1 *Evaluable lesions: measurable lesion and/or non-measurable lesion 6) Be willing to provide tissue; newly obtained endoscopic biopsy specimens or formalin-fixed, paraffin-embedded (FFPE) block specimens. 7) Female subjects of childbearing potential have a negative urine or serum pregnancy test within 7 days prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. It is allowed that the test at the same day at 7 days prior to enrollment. And male / female subjects of childbearing potential must be agree to use an adequate method of contraception starting with signing the informed consent through 120 days after the last dose of study medication. 8) Demonstrated adequate organ function as defined in following criteria. All screening labs should be performed within 7 days of enrollment. It is allowed that the labs at the same day at 7 days prior to enrollment. Note: Subject must not have taken transfusion, hematopoietic agent; G-CSF etc., and/or oxygen inhalation within 7 days before the screening labs. a. Absolute neutrophil count (ANC)>=1,500 /mm3 b. Platelets>=100,000 /mm3 c. Hemoglobin>=9.0 g/dL d. Serum total bilirubin<=2.0 mg/dL e. AST (SGOT) and ALT (SGPT)<=100 IU/L for subjects with liver metastases<=200 IU/L f. Serum creatinine<= 1.5 mg/dL; or if serum creatinine > 1.5 mg/dL, creatinine/clearance >=60 mL/min (Cockroft-Gault formula)
Key exclusion criteria	1) Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of study Day 1. 2) Has an active autoimmune disease that has required systemic treatment in past 2 years. 3) Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study Day 1. 4) Has known active central nervous system metastases and/or carcinomatous meningitis. 5) Has had prior anti-cancer monoclonal antibody chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or immunotherapy targeted to PD-1, PD-L1, PD-L2 within 4 weeks prior to Day 1 or OBP-301 study, who has not recovered from adverse events due to a previously administered agent. 6) Has a known additional malignancy that is progressing or requires active treatment. 7) Has received a live vaccine within 30 days of planned start of study therapy. 8) Has a known history of Human Immunodeficiency Virus. 9) Has known active Hepatitis B or Hepatitis C. 10) Has known history of, or any evidence of active, non-infectious pneumonitis. 11) Has an active infection requiring systemic therapy. 12) Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 13) Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. 14) Previous severe hypersensitivity to another monoclonal antibody 15) Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial,interfere with the subject's participation for the full duration of the trial,or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Target sample size	38

Research contact person
Name of lead principal investigator	1st name Toshihiko Middle name Last name Doi
Organization	National Cancer Center Hospital East
Division name	Department of Experimental Therapeutics
Zip code	277-8577
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba, Japan
TEL	04-7133-1111
Email	OBPem_core@east.ncc.go.jp

Public contact
Name of contact person	1st name Takashi Middle name Last name Kojima
Organization	National Cancer Center Hospital East
Division name	Department of GI Oncology
Zip code	277-8577
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
TEL	04-7133-1111
Homepage URL
Email	OBPem_core@east.ncc.go.jp

Sponsor
Institute	National Cancer Center Hospital East
Institute
Department

Funding Source
Organization	Oncolys BioPharma Inc.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)	Project of Translational and Clinical Research Core Centers

IRB Contact (For public release)
Organization	National Cancer Center Hospital Institutional Review Board
Address	Tsukiji 5-1-1, Chuo-ku, Tokyo
Tel	04-7133-1111
Email	irboffice@east.ncc.go.jp

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	岡山大学病院(岡山県)、国立がん研究センター東病院(千葉県)

Other administrative information
Date of disclosure of the study information	2017 Year 07 Month 31 Day

Related information
URL releasing protocol
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	Open public recruiting
Date of protocol fixation	2017 Year 05 Month 02 Day
Date of IRB	2017 Year 06 Month 21 Day
Anticipated trial start date	2017 Year 10 Month 01 Day
Last follow-up date	2022 Year 05 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 04 Month 12 Day
Last modified on	2020 Year 04 Month 14 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030917

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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