UMIN-CTR Clinical Trial

Basic information
Public title	Phase II trial of induction mFOLFOX6 plus Avastin followed by neoaduvant chemoradiotherapy with TS-1 for MRI-defined high-risk rectal cancer (IMPACT-RC)
Acronym	Phase II trial of induction mFOLFOX6 plus Avastin followed by neoadjuvant chemoradiotherapy with TS-1 for high-risk rectal cancer
Scientific Title	Phase II trial of induction mFOLFOX6 plus Avastin followed by neoaduvant chemoradiotherapy with TS-1 for MRI-defined high-risk rectal cancer (IMPACT-RC)
Scientific Title:Acronym	Phase II trial of induction mFOLFOX6 plus Avastin followed by neoadjuvant chemoradiotherapy with TS-1 for high-risk rectal cancer
Region	Japan

Condition
Condition	Resectable locally advanced rectal cancer
Classification by specialty	Gastroenterology Hematology and clinical oncology Gastrointestinal surgery Radiology Adult
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy and safety of induction mFOLFOX6 plus bevacizumab followed by neoaduvant chemoradiotherapy with S-1 for MRI-defined high-risk rectal cancer
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	pCR rate
Key secondary outcomes	Safety (proportion of adverse events and morbidity), R0 resection rate, Response rate, Proportion of clinical downstaging, Three-year recurrence free survival, Proportion of gastrointestinal perforation during the treatment

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	Preoperative administration of six courses mFOLFOX6 + bevacizumab (5mg) followed by 50.4Gy chemoradiation (1.8Gy x28) with S-1 (80-120mg daily on days 1-14 and 22-35)
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	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Rectal adenocarcinoma diagnosed pathologically at the Department of Pathology, Cancer Institute Hospital, Tokyo, Japan. 2) Patients with MRI and CT-defined locally advanced rectal cancer who meet either of the following clinical criteria. * Lateral lymph node metastasis and/or 4 or more mesorectal lymph node metastases (N2-3 as defined by the 7th edition of the Japanese Classification of Colorectal Carcinoma). * Lymph node metastasis along the proximal superior mesenteric artery (N2-3 as defined by the 6th edition of the Japanese Classification of Colorectal Carcinoma). * Tumors extending to within 1 mm of or beyond the mesorectal fascia (ie, CRM involved or threatened). * T3 low-lying tumors at or below the levators or T4 tumors invading to the levators (ie, abdominoperineal resection needed for R0 resection). * T4 tumors invading to surrounding structures or peritoneum. * Tumors extending 5 mm or more into perirectal fat. 3) Lower edge of tumors located at or below the lower edge of the second sacrum (Ra/Rb rectal cancer as defined by the 7th edition of the Japanese Classification of Colorectal Carcinoma). 4) R0 resection is possible before treatment. 5) No distant metastasis. 6) Performance Status (ECOG) 0 or 1. 7) No preceding preoperative radiotherapy, chemotherapy or hormonal therapies. 8) Function of major organs is well-preserved, including bone marrow, heart, lung and kidney. 9) Oral administration is possible. 10) Written informed consent is obtained.
Key exclusion criteria	1) Contraindication for either of S-1, Oxaliplatin, 5-FU, Leucovorin or Bevasizumab 2) Past history of severe hypersensitivity to the drugs 3) Past history of irradiation to the pelvis 4) Presence of infection with fever 5) Presence of severe morbidity such as heart failure, interstitial pneumonia, pulmonary fibrosis, uncontrollable diabetes, renal failure and liver failure. 6) Presence of sensory neuropathy 7) Presence or clinical manifestation of brain metastasis 8) Presence of diarrhea daily 9) Presence of ascites and/or pleural effusion which need aspiration 10) Presence of concomitant malignancy or past history of malignancy within five years 11) Female with pregnancy 12) Male who desire to keep fertility 13) Other inappropriate cases judged by doctors
Target sample size	43

Research contact person
Name of lead principal investigator	1st name Tsuyoshi Middle name Last name Konishi
Organization	The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Division name	Gastroenterological Surgery
Zip code	1358550
Address	3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan
TEL	03-3520-0111
Email	tkonishi-tky@umin.ac.jp

Public contact
Name of contact person	1st name Tsuyoshi Middle name Last name Konishi
Organization	The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Division name	Gastroenterological Surgery
Zip code	1358550
Address	3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan
TEL	03-3520-0111
Homepage URL
Email	tkonishi-tky@umin.ac.jp

Sponsor
Institute	The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Institute
Department

Funding Source
Organization	Takeda Science Foundation Sumitomo Mitsui Banking Corporation Japanese Foundation for Multidisciplinary Treatment of Cancer
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Address	Ariake 3-8-31, Koto-ku, Tokyo 135-8550, Japan
Tel	03-3520-0111
Email	naomasa.yamanojyo@jfcr.or.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

Other administrative information
Date of disclosure of the study information	2013 Year 08 Month 11 Day

Related information
URL releasing protocol
Publication of results	Partially published

Result
URL related to results and publications
Number of participants that the trial has enrolled	76
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	Completed
Date of protocol fixation	2012 Year 11 Month 05 Day
Date of IRB	2012 Year 11 Month 08 Day
Anticipated trial start date	2012 Year 11 Month 14 Day
Last follow-up date	2019 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	Recruiting of patients for the primary endpoint (pCR) has finished (n=43). Now we are recruiting patients for additional research of revealing proportion of GI perforatoin during the treatment as a secondary endpoint (n=78).

Management information
Registered date	2013 Year 08 Month 11 Day
Last modified on	2019 Year 07 Month 08 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000013413