UMIN-CTR Clinical Trial

Basic information
Public title	An exploratory study of PRecision dOsing of moLecular targeted agents based On therapeutic drug monitoriNG
Acronym	PROLONG study
Scientific Title	An exploratory study of PRecision dOsing of moLecular targeted agents based On therapeutic drug monitoriNG
Scientific Title:Acronym	PROLONG study
Region	Japan

Condition
Condition	1) Colorectal cancer 2) Gastrointestinal stromal tumors 3) Hepatocellular carcinoma 4) Renal cell carcinoma 5) Soft tissue sarcoma
Classification by specialty	Gastroenterology Hepato-biliary-pancreatic medicine Gastrointestinal surgery Hepato-biliary-pancreatic surgery Orthopedics Urology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	We will reveal the clinical usefulness of pharmacokinetically (PK)-guided dosing strategy of molecular targeted agents (regorafenib, pazopanib, and axitinib) in the determination of a tolerable maintenance dose for prolonged duration of treatment in advanced cancer patients. In addition, we will explore associations between drug exposure and clinical efficacy and safety. Furthermore, we will clarify the impact of genetic polymorphisms on the interindividual variability in plasma and urine drug concentrations.
Basic objectives2	PK,PD
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	To reveal the clinical benefit of therapeutic drug monitoring (TDM) of molecular targeted agents (regorafenib, pazopanib, and axitinib) in terms of prolonged duration of treatment by determining a tolerable maintenance dose in individual patients, compared with the empirical approach based only on clinical and laboratory findings.
Key secondary outcomes	1) To explore associations between drug exposure and clinical efficacy and safety. 2) To clarify the impact of genetic polymorphisms on the interindividual variability in plasma and urine drug concentrations.

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	1) PK profiles of regorafenib and its metabolites (M-2/M-5 and M-7/M-8) at week 1, 2, and 3 during the first cycle will be examined. In addition, the subsequent drug concentrations after dose adaptation by taking individual drug concentration and the target trough level (1400 ng/mL) into consideration will be evaluated. 2) PK profile of pazopanib at steady state after start of treatment will be examined. In addition, the subsequent drug concentrations after dose adaptation by taking individual drug concentration and the target trough level (20.5 mcg/mL) into consideration will be evaluated. 3) PK profile of axitinib at steady state after start of treatment will be examined. In addition, the subsequent drug concentrations after dose adaptation by taking individual drug concentration and historical PK data into consideration will be evaluated.
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) All patients treated with regorafenib 2) All patients treated with pazopanib 3) All patients treated with axitinib 4) Patients who can give written informed consent
Key exclusion criteria	1) Patients who are currently participating in or will be enrolled in clinical trials 2) Patients receiving molecular targeted therapy as an off-label use
Target sample size	50

Research contact person
Name of lead principal investigator	1st name Masahide Middle name Last name Fukudo
Organization	Asahikawa Medical University
Division name	Department of Hospital Pharmacy and Pharmacology
Zip code	078-8510
Address	2-1-1-1 Midorigaokahigashi, Asahikawa 078-8510, Japan
TEL	0166-69-3482
Email	mfukudo@asahikawa-med.ac.jp

Public contact
Name of contact person	1st name Masahide Middle name Last name Fukudo
Organization	Asahikawa Medical University
Division name	Department of Hospital Pharmacy and Pharmacology
Zip code	078-8510
Address	2-1-1-1 Midorigaokahigashi, Asahikawa 078-8510, Japan
TEL	0166-69-3482
Homepage URL
Email	mfukudo@asahikawa-med.ac.jp

Sponsor
Institute	Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University
Institute
Department

Funding Source
Organization	None
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	Asahikawa Medical University Research Ethics Committee
Address	2-1-1-1 Midorigaokahigashi, Asahikawa 078-8510, Japan
Tel	0166-68-2297
Email	rs-kk.g@asahikawa-med.ac.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	2019 Year 03 Month 11 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 05 Month 27 Day
Date of IRB	2015 Year 05 Month 27 Day
Anticipated trial start date	2015 Year 05 Month 27 Day
Last follow-up date	2024 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2020 Year 03 Month 31 Day

Other
Other related information	Outcome measures to be studied: 1) Objective response rate 2) Progression-free survival 3) Overall survival 4) Duration of treatment 5) Frequency of adverse events

Management information
Registered date	2019 Year 03 Month 11 Day
Last modified on	2020 Year 04 Month 30 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041195