UMIN-CTR Clinical Trial

Basic information
Public title	A phase I/II study for the safety and efficacy of Panitumumab in combination with TAS-102 for patients with RAS wild-type metastatic colorectal cancer refractory to standard chemotherapy
Acronym	A phase I/II study for the safety and efficacy of Panitumumab in combination with TAS-102 for patients with metastatic colorectal cancer (APOLLON study)
Scientific Title	A phase I/II study for the safety and efficacy of Panitumumab in combination with TAS-102 for patients with RAS wild-type metastatic colorectal cancer refractory to standard chemotherapy
Scientific Title:Acronym	A phase I/II study for the safety and efficacy of Panitumumab in combination with TAS-102 for patients with metastatic colorectal cancer (APOLLON study)
Region	Japan

Condition
Condition	unresectable advanced colorectal cancer
Classification by specialty	Gastroenterology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Phase I part: To judge the move to next cohort with evaluating the safety and tolerability based on DLT ratio. Phase II part: Progression free survival rate at 6 months PFS. The period will be determined from the day of enrollment.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I,II

Assessment
Primary outcomes	Phase I: DLT rate (1st course: 4 weeks) Phase II: PFS rate at 6 months
Key secondary outcomes	OS: Overall survival PFS: Progression free survival RR: Response rate DOR: Duration of response DCR: Disease control rate TTF: Time to treatment failure <Safety>Adverse events

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	Panitumumab+TAS-102 -Panitumumab 6mg/kg/ q2w -TAS-102 35mg/m2 (Day1-5, Day8-12)
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	75 years-old >
Gender	Male and Female
Key inclusion criteria	(1)Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol. (2)Patients who have given written consent to take part in the study after detailed explanation of the study prior to enrollment (3)Aged 20 to 75 years at the time of informed consent (4)Patients with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer) (5)Patients with lesion(s) that can be evaluated. It is not essential to be evaluated the tumor according to the RECIST ver. 1.1. (6)Patients who have received chemotherapies for metastatic colorectal cancer and are refractory to or failing those chemotherapies* including; fluoropyrimidines, irinotecan, oxaliplatin, and an anti-vascular endothelial growth factor (VEGF) agent. (7)Patients classified as KRAS/NRAS wild-type by KRAS/NRAS testing. (8)Patients are able to take medications orally. (9)Patients who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment Neutrophil count 1500/microL Platelet count 100000/microL Hemoglobin 8.0 g/dL Total bilirubin 1.5 mg/dL AST 100 IU/L ( 200 IU/L if liver metastases are present) ALT 100 IU/L ( 200 IU/L if liver metastases are present) Serum creatinine 1.5 mg/dL (10)ECOG performance status (PS) of 0 or 1 (11)Life expectancy of 3 months (90 days) or more after enrollment
Key exclusion criteria	(1)Has received anti-EGFR antibodies (cetuximab or panitumumab), regorafenib, or TAS-102. (2)Has had treatment with radiotherapy and/or chemotherapy within 2 weeks (14 days) prior to study drug administration (except for limited field radiation in order to rescue of pain). (3)Known brain metastasis or strongly suspected of brain metastasis (4)Synchronous cancers or metachronous cancers with a disease-free period of 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection (esophageal, stomach, and cervical cancer, non-melanoma skin cancer, bladder cancer, etc.). (5)Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.) (6)Patients who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy (7)Any investigational agent received within prior 4 weeks (28 days). (8)Disease requiring systemic steroids for treatment (excluding topical steroids) (9)History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.) (10)Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhoea (incapacitating symptoms despite adequate treatment. (11)Serious drug hypersensitivity (without allergy to oxaliplatin) (12)Local or systemic active infection requiring treatment, or fever indicating infection (13)NYHA class II or higher heart failure or serious heart disease (14)Active hepatitis B (15)Known HIV infection (16)Peripheral neuropathy of Grade 2 or greater by CTCAE (Japanese edition JCOG version 4.03) (17)Known BRAF mutation (18)Other patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study
Target sample size	52

Research contact person
Last name of lead principal investigator	1st name Middle name Last name Kensei Yamaguchi/Takeshi Kato
Organization	Cancer Institute Hospital/National Hospital Organization Osaka National Hospital
Division name	Gastroenterological medicine/Surgery
Zip code
Address	3-8-31 Ariake, Koto-ku, Tokyo /2-1-14, Hoenzaka, Chuo-ku, Osaka City
TEL	0120-086723
Email	apollon@medical-bs24.com

Public contact
1st name of contact person	1st name Middle name Last name Contact for Clinical Trial Information
Organization	Takeda Pharmaceutical Company Limited
Division name	Contact for Clinical Trial Information
Zip code
Address	12-10 Nihonbashi 2-chome Chuo-ku Tokyo Japan
TEL	0120-086723
Homepage URL
Email	apollon@medical-bs24.com

Sponsor
Institute	Takeda Pharmaceutical Company Limited
Institute
Department

Funding Source
Organization	Takeda Pharmaceutical Company Limited
Organization
Division
Category of Funding Organization	Profit organization
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	YES
Study ID_1	NCT02613221
Org. issuing International ID_1	A service of the U.S. National Institutes of Health
Study ID_2	JapicCTI-153076
Org. issuing International ID_2	Japan Pharmaceutical Information Center
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 11 Month 20 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	Completed
Date of protocol fixation	2015 Year 10 Month 27 Day
Date of IRB	2018 Year 03 Month 30 Day
Anticipated trial start date	2015 Year 12 Month 07 Day
Last follow-up date	2018 Year 03 Month 30 Day
Date of closure to data entry	2018 Year 03 Month 30 Day
Date trial data considered complete	2018 Year 07 Month 11 Day
Date analysis concluded	2018 Year 10 Month 23 Day

Other
Other related information

Management information
Registered date	2015 Year 11 Month 20 Day
Last modified on	2019 Year 05 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000022954