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Trial registered on ANZCTR


Registration number
ACTRN12610000898055
Ethics application status
Approved
Date submitted
15/10/2010
Date registered
21/10/2010
Date last updated
2/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The use of non invasive methods to predict drug handling and toxicity of Irinotecan
Scientific title
The utility of genomics and functional imaging to predict Irinotecan pharmacokinetics and pharmacodynamics: The PREDICT Irinotecan Study
Secondary ID [1] 252874 0
PMCC Protocol No 10/55
Universal Trial Number (UTN)
Trial acronym
The PREDICT IR study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally advanced, recurrent or metastatic colorectal adenocarcinoma 258404 0
Condition category
Condition code
Cancer 258570 258570 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Standard treatment of FOLFIRI or FOLFIRI-Avastin regimen for the period of 8 weeks
The Irinotecan will be given over 90 minutes followed by Leucovorin given intravenously over 2 hours and immediately followed by Avastin given over 1 hour if the doctor decides to combine it with FOLFIRI. 5FU will be given intravenously by rapid injection and then 5FU will be given over 46 hrs through a pump connected to the PORT/PICC. Patient will be educated about the care of the PICC or PORT and the pump. The pump will be disconnected at the end of the 46 hours performed at patient home.

Total duration of the study 4 years
Intervention code [1] 257401 0
Not applicable
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259415 0
Response assessment in the first 4 courses of treatment
using computed tomography (CT) scan and/or magnetic resonance imaging (MRI) and/or positron emission tomography (PET) and/or X-Ray and clinical examination.
Timepoint [1] 259415 0
8 weeks
Primary outcome [2] 259418 0
Correlations between functional imaging and PK
and between functional imaging and Toxicity
Associations will be assessed to examine the strength and direction of the linear relationship between HFI with PK and toxicity parameters. The Pearson correlation coefficient (for normally distributed variables) or nonparametric Spearman rank correlation (for any non-normally distributed variables) will be calculated with the correlation (r2) and p-value reported. Linear regression models to predict PK parameters from HFI parameters will be fitted to estimate the relationship between pairs of parameters identified as having a significant correlation coefficient. Logistic regression will be used to assess whether HFI parameters can predict presence or absence of grade delayed diarrhoea and neutropenia.
Timepoint [2] 259418 0
In the 4th year of the project
Primary outcome [3] 259419 0
Correlations of genetic factors, with PK, toxicity and response
SNP genotypes will be assessed for deviations from Hardy-Weinberg equilibrium. Fisher's exact test or Pearson's chi-square test will be used, as appropriate, to assess the association between SNP genotypes with toxicity and objective response in 2 degree of freedom tests. Linear and logistic regressions will be used to assess the relationship between the number of minor alleles at each SNP with pharmacokinetic, toxicity and response parameters, as appropriate, in 1 degree of freedom tests.
Timepoint [3] 259419 0
In the 4th year of the project
Secondary outcome [1] 265961 0
Nil
Timepoint [1] 265961 0
Nil

Eligibility
Key inclusion criteria
Histologically/cytologically confirmed locally advanced, recurrent or metastatic colorectal adenocarcinoma not amenable to surgery or radiation therapy with curative intent, eligible for first-line or second-line chemotherapy with Irinotecan-5FU (FOLFIRI regimen or FOLFIRI-Bevacizumab [Avastin]); measurable or evaluable disease, adequate hepatic, bone marrow and renal function, Eastern Cooperative Oncology Group (ECOG) 2 or less, life expectancy greater than 12 weeks, written informed consent for the study and its associated procedures.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol or compromises the patient's ability to give informed consent.
Female patients who are pregnant or breast-feeding.
Any unresolved toxicity greater than NCI-CTC Grade 2 from previous anti-cancer therapy, active liver disease (e.g. chronic active hepatitis, cirrhosis), known diagnosis of human immunodeficiency virus (HIV) infection or Gilbert’s syndrome, prior severe reaction of fluoropyrimidine therapy, known sensitivity to 5-FU or deficit of dihydropyrimidine-dehydrogenase (DPD)

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment postcode(s) [1] 3303 0
3002
Recruitment postcode(s) [2] 3304 0
3050
Recruitment postcode(s) [3] 3305 0
3084
Recruitment postcode(s) [4] 3306 0
3011
Recruitment postcode(s) [5] 3307 0
3128
Recruitment postcode(s) [6] 3308 0
3199
Recruitment postcode(s) [7] 3309 0
5042
Recruitment postcode(s) [8] 3310 0
5011
Recruitment postcode(s) [9] 3311 0
2065
Recruitment postcode(s) [10] 3312 0
2217
Recruitment postcode(s) [11] 3313 0
2050
Recruitment postcode(s) [12] 3328 0
2139

Funding & Sponsors
Funding source category [1] 257837 0
Government body
Name [1] 257837 0
National Health and Medical Research Council of Australia
Address [1] 257837 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 257837 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
St Andrew's Place, East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 257048 0
None
Name [1] 257048 0
Address [1] 257048 0
Country [1] 257048 0
Other collaborator category [1] 251559 0
Individual
Name [1] 251559 0
Assoc Prof. Michael Jefford
Address [1] 251559 0
Division of Haematology and Medical Oncology
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, 3002, VIC
Country [1] 251559 0
Australia
Other collaborator category [2] 251560 0
Individual
Name [2] 251560 0
Prof J Zalcberg
Address [2] 251560 0
Division of Haematology and Medical Oncology
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, 3002, VIC
Country [2] 251560 0
Australia
Other collaborator category [3] 251561 0
Individual
Name [3] 251561 0
Dr C Cullinane
Address [3] 251561 0
Translational Research Laboratory
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, 3002, VIC
Country [3] 251561 0
Australia
Other collaborator category [4] 251562 0
Individual
Name [4] 251562 0
Assoc Prof Ian Campbell
Address [4] 251562 0
Cancer Genetics
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, 3002, VIC
Country [4] 251562 0
Australia
Other collaborator category [5] 251563 0
Individual
Name [5] 251563 0
Assoc Prof. N Tebbutt
Address [5] 251563 0
Dept of Medical Oncology
Austin Hospital
Studley Road, Heidelberg Heights, VIC, 3084
Country [5] 251563 0
Australia
Other collaborator category [6] 251564 0
Individual
Name [6] 251564 0
Prof A Scott
Address [6] 251564 0
Dept of Nuclear Medicine and Ludwig Institute
Studley Road, Heidelberg Heights, VIC, 3084
Country [6] 251564 0
Australia
Other collaborator category [7] 251565 0
Individual
Name [7] 251565 0
Assoc Prof L Lipton
Address [7] 251565 0
Medical Oncology and Clinical Haematology Unit
Western Hospital
Gordon Street, Footscray, VIC, 3011
Country [7] 251565 0
Australia
Other collaborator category [8] 251566 0
Individual
Name [8] 251566 0
Dr J Desai
Address [8] 251566 0
Dept of Medical Oncology
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, VIC, 3002
Country [8] 251566 0
Australia
Other collaborator category [9] 251567 0
Individual
Name [9] 251567 0
Dr Vinod Ganju
Address [9] 251567 0
Department of Medical Oncology
Peninsula Oncology Centre
24-28 Frankston-Flinders Road, Frankston, VIC, 3199
Country [9] 251567 0
Australia
Other collaborator category [10] 251568 0
Individual
Name [10] 251568 0
Dr Phillip Parente
Address [10] 251568 0
Department of Medical Oncology
Box Hill Hospital
Nelson Road, Box Hill, VIC, 3128
Country [10] 251568 0
Australia
Other collaborator category [11] 251569 0
Individual
Name [11] 251569 0
Assco Prof Joe McKendrick
Address [11] 251569 0
Department of Medical Oncology
Box Hill Hospital
Nelson Road, Box Hill, VIC, 3128
Country [11] 251569 0
Australia
Other collaborator category [12] 251570 0
Individual
Name [12] 251570 0
Assoc Prof Sue-Anne McLachlan
Address [12] 251570 0
St Vincent's Hospital
41 Victoria Parade, Fitzroy, VIC, 3065
Country [12] 251570 0
Australia
Other collaborator category [13] 251571 0
Individual
Name [13] 251571 0
Prof S Clarke
Address [13] 251571 0
Dept of Medicine and Medical Oncology
Concord Hospital
Hospital Road, Concord, NSW, 2139
Country [13] 251571 0
Australia
Other collaborator category [14] 251572 0
Individual
Name [14] 251572 0
Assoc Prof L Hovarth
Address [14] 251572 0
Dept of Medical Oncology
Royal Prince Alfred Hospital
Missenden Road, Camperdown, NSW, 2050
Country [14] 251572 0
Australia
Other collaborator category [15] 251573 0
Individual
Name [15] 251573 0
Dr W Liauw
Address [15] 251573 0
Dept of Medical Oncology
St Georges Hospital
Gray Street, Kogarah, NSW, 2217
Country [15] 251573 0
Australia
Other collaborator category [16] 251574 0
Individual
Name [16] 251574 0
Assoc Prof M Links
Address [16] 251574 0
Dept of Medical Oncology
Royal North Shore Hospital
Pacific Highway, St Leonards, NSW, 2065
Country [16] 251574 0
Australia
Other collaborator category [17] 251575 0
Individual
Name [17] 251575 0
Dr N Pavlakis
Address [17] 251575 0
Dept Medical Oncology
Queen Elizabeth Hospital
Woodville Road, Woodville, SA, 5011
Country [17] 251575 0
Australia
Other collaborator category [18] 251576 0
Individual
Name [18] 251576 0
Assoc Prof T Price
Address [18] 251576 0
Dept Medical Oncology
Flinders Medical Centre
Flinders Drive, Bedford Park, SA, 5042
Country [18] 251576 0
Australia
Other collaborator category [19] 251577 0
Individual
Name [19] 251577 0
Dr C Karapetis
Address [19] 251577 0
Dept of Medical Oncology
Flinders Medical Centre
Flinders Drive, Bedford Park, SA, 5042
Country [19] 251577 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259909 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 259909 0
Level 4, 10 St Andrews Place
East Melbourne, Victoria, 3002
Ethics committee country [1] 259909 0
Australia
Date submitted for ethics approval [1] 259909 0
07/07/2010
Approval date [1] 259909 0
31/08/2010
Ethics approval number [1] 259909 0
PMCC Protocol No 10/55

Summary
Brief summary
Observational pharmacology/pharmacogenomic/imaging study in patients receiving standard FOLFIRI ± Avastin for advanced incurable colorectal cancer.
Patients will undergo baseline nuclear hepatic functional imaging with IDA scans and bloods will be taken for metabolic/pharmacodynamic pharmacogenomics.
Bloods will be taken for Irinotecan PK in course 1.
Toxicities will be documented in the first 4 cycles and patients will be restaged at the end of cycle 4 (i.e. 8 weeks).
No trial involvement beyond 4 cycles is required and treatment beyond this point will be at the discretion of the treating clinician.
Trial website
Trial related presentations / publications
Abstract published in the ESMO 2017 Congress Abstract Book, a supplement to the official ESMO journal Annals of Oncology.
Public notes

Contacts
Principal investigator
Name 31773 0
A/Prof Michael Michael
Address 31773 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Australia
Country 31773 0
Australia
Phone 31773 0
+61 3 8559 7860
Fax 31773 0
Email 31773 0
Michael.Michael@petermac.org
Contact person for public queries
Name 15020 0
A/Prof Assoc Prof M Michael
Address 15020 0
Division of Haematology and Medical Oncology
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, 3002, VIC
Country 15020 0
Australia
Phone 15020 0
+61 3 96561159
Fax 15020 0
+61 3 96561408
Email 15020 0
Michael.Michael@petermac.org
Contact person for scientific queries
Name 5948 0
A/Prof Assoc Prof M Michael
Address 5948 0
Division of Haematology and Medical Oncology
Peter MacCallum Cancer Centre
St Andrew's Place, East Melbourne, 3002, VIC
Country 5948 0
Australia
Phone 5948 0
+61 3 96561159
Fax 5948 0
+61 3 96561408
Email 5948 0
Michael.Michael@petermac.org

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary