UMIN-CTR Clinical Trial

Basic information
Public title	A phase II study to confirm the effectiveness of a sequence therapy consisted induction therapy (Capecitabin or S-1 or sLV/5-FU plus Bevacizumab) and following therapy (induction therapy + oxaliplatin) for unresectable advanced/recurrent colo-rectal cancer (OGSG 1107)
Acronym	A phase II study to confirm the effectiveness of a sequence therapy consisted induction therapy (Capecitabin or S-1 or sLV/5-FU plus Bevacizumab) and following therapy (induction therapy+oxaliplatin) for unresectable advanced/recurrent colo-rectal cancer
Scientific Title	A phase II study to confirm the effectiveness of a sequence therapy consisted induction therapy (Capecitabin or S-1 or sLV/5-FU plus Bevacizumab) and following therapy (induction therapy + oxaliplatin) for unresectable advanced/recurrent colo-rectal cancer (OGSG 1107)
Scientific Title:Acronym	A phase II study to confirm the effectiveness of a sequence therapy consisted induction therapy (Capecitabin or S-1 or sLV/5-FU plus Bevacizumab) and following therapy (induction therapy+oxaliplatin) for unresectable advanced/recurrent colo-rectal cancer
Region	Japan

Condition
Condition	Colo-rectal cancer
Classification by specialty	Gastroenterology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The purpose of this study is to know the feasibility and effectiveness of a sequence therapy consisted by the induction therapy (5-FU or Capecitabin or S-1 plus Bevacizumab) and the following therapy (induction therapy plus Oxaliplatin) for unresectable advanced/recurrent colo-rectal cancer
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Progression Free Survival between the start of treatment and Progression of second line treatment (1st +2nd PFS)
Key secondary outcomes	Progression Free Survival of 1st line treatment Response Rate Disease Control Rate Overall Survival Adverse Events (Incidence and Grades) Medicines with good response during overall treatment by KRAS status

Base
Study type	Interventional

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

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Capecitabin is administered between day 1 and 14 orally followed by 7 days rest. Bevacizumab is administered 7.5mg/kg by intra-venous infusion on day 1. One course takes 3 weeks. After 1st-PD, 130mg/m2 of oxaliplatin is added by intra-venous infusion on day 1 of this three week regimen.
Interventions/Control_2	S-1 is administered between day 1 and 14 orally followed by 7 days rest. Bevacizumab is administered 7.5mg/kg by intra-venous infusion on day 1. One course takes 3 weeks. After 1st-PD, 130mg/m2 of oxaliplatin is added by intra-venous infusion on day 1 of this three week regimen.
Interventions/Control_3	A continuous 5-FU administration (2400mg/m2 by 46 hours) is done after LV (200mg/m2) and following bolus 5-FU (400mg/m2) are administered intra-venously. Bevacizumab is administered 5mg/kg by intra-venous infusion on day 1. One course takes 2 weeks. After 1st-PD, 85mg/m2 of oxaliplatin is added by intra-venous infusion on day 1 of this two week regimen. Bevacizumab is administered 5mg/kg by intra-venous infusion on day 1 of this two week regimen.
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	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1)Histologically proven colon cancer or rectal cancer 2)with lesions which can be estimated by RECIST criteria version 1.1 3)with unresectable factors 4)without any symptoms which influence to lives 5)age between 20 and 75 years old 6)PS : 0-2 7)without any prior chemotherapy except fluoro-pyrimidine over 6 months ago 8)with enough rest period after prior modality : a)More than 4 weeks of surgical treatment b)More than 4 weeks of hormone therapy or immunotherapy c)More than 4 weeks of cytokine or BMR 9)with good function of important organs a)WBC : 3,000/mm3 <= and <= 10,000/mm3 b)neutrophil : 1,500/mm3 <= c)Hemoglobin : 9.0g/dL <= d)Platelet : 100,000/mm3 <= e)AST/ALT : within 3 times of normal range of the hospital f)Total bilirubin : 1.2mg/dL >= g)s-Creatinine : 1.2mg/dL >= h)ALP : 300U/L >= i)Creatinine clearance >= 50mL/min male : [(140-age) x B.W.(kg)]/[(72 x s-crearinine(mg/dL)] female : [(140-age) x B.W.(kg) x 0.85]/[(72 x s-crearinine(mg/dL)] 10)patients expected more than 8 weeks survival 11)with written informed consent
Key exclusion criteria	1)with symptoms due to brain metastasis 2)with uncontrollable diarrhea 3)with difficulty on oral intake due to intestinal paralysis or obstruction 4)with infectious disease or febrile condition 5)HBs Ag (+) 6)with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, pulmonary emphysema etc.) 7)with severe diseases (uncontrollable DM, heart failure severe than NYHA III, renal failure and/or hepatic failure) 8)pregnant and/or nursing women, or women who expect pregnancy 9)with metastatic meningitis, uncontrollable convulsion, and/or mental disorder 10)with a more than grade 1 neural disorder 11)with a condition intolerant to medicines in this regimen (5-FU, Xeloda, TS-1, Avastine or Erplat) 12)with a history of allergy against 5-Fu, Capecitabine or TS-1 13)with a history of some chemotherapy and/or therapy including a VEGF antagonist for unresectable advanced/recurrent colon cancer 14)with a history of embolism, brain infarction (except Lacuna infarction) or pulmonary infarction 15)under easy bleeding condition due to some diseases or medicines (except low dose aspirin) 16)with a history of thoracic surgery or abdominal surgery 28 days ago except reservoir surgery 17)with active wounds 18)with a history of bloody spit more than 2.5mL 19)any other patient whom the physician in charge of the study judges to be unsuitable
Target sample size	66

Research contact person
Name of lead principal investigator	1st name Middle name Last name Masahiro Goto
Organization	Osaka Medical College Hospital
Division name	Chemotherapy Center
Zip code
Address	2-7, Daigakucho, takatsuki, Osaka
TEL	072-683-1221
Email	in2030@poh.osaka-med.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Motoki Yoshida
Organization	Chemotherapy Center
Division name	Department of surgery
Zip code
Address	2-7, Daigakucho, takatsuki, Osaka
TEL	072-366-0221
Homepage URL
Email	ctc004@poh.osaka-med.ac.jp

Sponsor
Institute	Osaka Gastrointestinal cancer chemotherapy Study Group(OGSG)
Institute
Department

Funding Source
Organization	Osaka Clinical Study Supporting Organization
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization
Address
Tel
Email

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	大阪医科大学（大阪府）、大阪医療センター（大阪府）、市立貝塚病院（大阪府）

Other administrative information
Date of disclosure of the study information	2012 Year 01 Month 04 Day

Related information
URL releasing protocol	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021627/
Publication of results	Published

Result
URL related to results and publications	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021627/
Number of participants that the trial has enrolled	19
Results	The median 1st PFS and 2nd PFS were 12.8 months (95% confidence interval {CI] 10.4-26.7) and 19.1 months (95% CI 16.1-not reached [NR] months), respectively. The median 1st PFS C-group (Capecitabine + bevacizumab): 17.2 months (95% CI: 11.1 - NR) S-group (S-1 + bevacizumab): 10.8 months (95% CI: 10.4 - NR) F-group(LV/5-FU + bevacizumab): 11.2 months (95% CI: 7.8 - NR)
Results date posted	2022 Year 11 Month 06 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2022 Year 02 Month 15 Day
Baseline Characteristics	The mCRC patients with histologically confirmed adenocarcinoma with evaluable lesions
Participant flow	From December 2, 2011, to February 18, 2015, a total of 19 patients were enrolled. 4 patients were allocated to the C-group, 10 to the S-group, and 5 to the F-group.
Adverse events	Initial Therapy Toxicities associated with the initial therapy are neutropenia and thrombocytopenia of all grades were observed in 63% and 47%, respectively. The hematologic toxicities of grade >=3 included thrombocytopenia (5%) and neutropenia (5%). The nonhematologic toxicities of grade >=3 included anorexia (21%), proteinuria (21%), diarrhea (5%), nausea (5%), fatigue (5%), hypertension (47%), skin ulceration (5%), and thromboembolic events (5%). Subsequent Therapy Anemia, neutropenia, and thrombocytopenia of any grades were observed in 78, 66, and 66%, respectively. The hematologic toxicities of grade >=3 included leukopenia (11%) and neutropenia (11%). Nonhematologic toxicities of grade >=3 included anorexia (22%), hypertension (22%), febrile neutropenia (11%), and peripheral neuropathy (11%).
Outcome measures	The primary endpoint of the study was PFS between the start of enrollment and the progression of second-line treatment (2nd PFS) based on the full analysis set. The secondary endpoints were PFS of first-line treatment, overall response rate, OS, and safety.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2011 Year 10 Month 31 Day
Date of IRB	2011 Year 07 Month 04 Day
Anticipated trial start date	2011 Year 12 Month 02 Day
Last follow-up date	2017 Year 02 Month 17 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2017 Year 05 Month 29 Day

Other
Other related information

Management information
Registered date	2012 Year 01 Month 03 Day
Last modified on	2022 Year 11 Month 06 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008190