UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase II study of TAS-102 plus bevacizumab as maintenance therapy after induction chemotherapy with bevacizumab, oxaliplatin, and fluoropyrimidine in patients with metastatic colorectal cancer
Title of the study (Brief title)	Switch Maintenance Study
Region	Japan

Condition
Condition	Colorectal cancer
Classification by specialty	Gastroenterology Hematology and clinical oncology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	We conduct a first line induction chemotherapy with bevacizumab, oxaliplatin, and fluoropyrimidine in patients with metastatic colorectal cancer. Induction therapy will be stop systematically for 3 to 4 months then; the chemotherapy switch to TAS-102 plus bevacizumab. Aim of this study is to evaluate efficiency and safety of TAS-102 plus bevacizumab as maintenance therapy.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Progression free survival
Key secondary outcomes	Overall survival, Response rate, Disease control rate, Rechallenge rate of oxaliplatin, Safety; periods of maintenance therapy, dose intensity, adverse event, total dose of oxaliplatin

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	TAS-102 plus Bevacizumab TAS-102 35 mg/time, twice a day, oral intake Day1-5,8-12 Bevacizumab venous injection, 5.0 mg/kg Day1,15 Patients will continue study treatment until disease progression
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) Historical or cytological documentation of adenocarcinoma of the colon or rectum 2) First line chemotherapy and non-resectable advanced colorectal cancer. If patients were performed adjuvant chemotherapy, the period until first line chemotherapy has to be at least 6 months. 3) Male or female patients >= 20 4) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 5) Adequate bone marrow, liver and renal functions as assessed by the following laboratory requirements conducted within 14 days of starting study treatment: 1. Absolute neutrophil count >= 1500 /mm3 2. Hemoglobin >= 9.0 g/dl 3. Platelet >=100000 /mm3 4. Total bilirubin <=1.5 ml/dl 5. AST and ALT <=100 IU/l 6. Creatinine <= 1.5 mg/dl 6) Life expectancy of at least 90 days. 7) Patients must have measurable or non measurable disease according to RECIST version 1.1 8) Induction chemotherapy was done by CapeOX+Bevacizumb or FOLFOX+Bevacizumab. Except the induction therapy done by other approved standard therapies which include irinotecan or anti-EGFR drug. 9) Conduct a first line induction chemotherapy with bevacizumab, oxaliplatin, and fluoropyrimidine. Induction therapy will be stop systematically for 3 to 4 months then; the chemotherapy switch to TAS-102 plus bevacizumab; expected oxaliplatin dose is 610 to 680 mg/M2. 10) Confirmed the disease control; CR/PR/SD by each image after induction therapy. 11) Signed informed consent obtained before any study specific procedures. Patients must be able to understand and willing to sign a written informed consent.
Key exclusion criteria	1) Prior treatment with TAS-102 and Bevacizumab. 2) Previous or concurrent cancer that is distinct in primary site or histology form colorectal cancer within 1 years prior to EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta, Tis and T1]. 3) Major surgical procedure within 28 days before start of study medication. 4) Pregnant or breast-feeding patients. Woman of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment. 5)Congestive heart failure >=NYHA class 2. 6) Unstable angina, new-onset angina. Myocardial infarction less than 6 months before start of study medication. 7)Uncontrolled hypertension. 8) Pleural effusion or ascites with dyspnea higher than CTCAE v4.0 grade 2. 9) Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication. 10) Known history of HIV infection, or chronic hepatitis B or C. 11) Symptomatic metastatic brain or meningeal metastasis. 12) Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event >= CTCAE v4.0 Grade 3 within 4 weeks of start of study medication. 13) Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. 14) Persistant proteinuria of CTCAE v4.0 Grade 3 or higher. 15) Patients unable to swallow oral medications. 16) Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. 17) Non-healing wound, ulcer, or bone fracture. 18) Unsolved toxicity higher than CTCAE v4.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity <= Grade 2. 19) A responsible doctor has confirmed the candidate should be excluded from this study.
Target sample size	55

Research contact person
Name of lead principal investigator	Katsuya Ohta
Organization	Higashiosaka city medical center
Division name	Department of Gastroenterological surgery
Address	Nishiiwata 3-4-5, Higashiosaka city, Osaka, Japan
TEL	06-6781-5101
Email	ohta-k@higashiosaka-hosp.jp

Public contact
Name of contact person	Katsuya Ohta
Organization	Higashiosaka city medical center
Division name	Department of Gastroenterological surgery
Address	Nishiiwata 3-4-5, Higashiosaka city, Osaka, Japan
TEL	06-6781-5101
Homepage URL
Email	ohta-k@higashiosaka-hosp.jp

Sponsor
Institute	Multicenter Clinical Study Group of Osaka, Colorectal Cancer Treatment Group
Institute
Department

Funding Source
Organization	Non
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

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

Other administrative information
Date of disclosure of the study information	2018 Year 02 Month 16 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2017 Year 11 Month 29 Day
Anticipated trial start date	2017 Year 12 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2018 Year 02 Month 15 Day
Last modified on	2018 Year 02 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035746