Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000399695
Ethics application status
Approved
Date submitted
31/03/2014
Date registered
14/04/2014
Date last updated
13/12/2018
Date data sharing statement initially provided
13/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
INTEGERATE: Is Integrated Geriatric Assessment and Treatment Effective in older adults with cancer receiving cytotoxic chemotherapy, targeted therapy or immunotherapy? A Randomised Controlled Study
Scientific title
A randomised controlled study comparing the effectiveness and cost-effectiveness of integrated oncogeriatric care with standard oncology care in improving quality of life in adults aged 70 years and older with cancer receiving cytotoxic chemotherapy, targeted therapy or immunotherapy.
Secondary ID [1] 284332 0
None
Universal Trial Number (UTN)
U1111-1154-8838
Trial acronym
INTEGERATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer in older adults 291487 0
Condition category
Condition code
Cancer 291853 291853 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Integrated oncogeriatric care

Integrated oncogeriatric care consists of comprehensive geriatric assessment and management, integrated with standard oncology care. In addition to seeing their oncologists, participants receiving integrated oncogeriatric care will have a comprehensive assessment and management by a consultant physician in geriatric medicine within 3 weeks from randomisation, followed by reviews at approximately 12 weeks and 24 weeks from randomisation. After 24 weeks from randomisation, participants in the intervention arm may continue to receive integrated oncogeriatric care but will not be required to complete further study assessments.
Intervention code [1] 289053 0
Early detection / Screening
Intervention code [2] 289173 0
Treatment: Other
Comparator / control treatment
Standard oncology care

This involves standard care as provided by their oncologists, including chemotherapy.
Control group
Active

Outcomes
Primary outcome [1] 291765 0
The Trial Outcome Index, which consists of the linear transformation from 0 to 100 of the unweighted summated scores of the physical functioning, role functioning and social functioning scales of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire, and the mobility scale of the EORTC QLQ-ELD14 questionnaire.
Timepoint [1] 291765 0
Baseline, and at 12, 18 and 24 weeks following randomisation
Secondary outcome [1] 307454 0
Quality of life, as assessed using the EORTC QLQ-C30 v3.0, EORTC QLQ-ELD14 and EQ-5D-5L
Timepoint [1] 307454 0
EORTC QLQ-C30 and QLQ-ELD14: baseline, and at 12 and 24 weeks following randomisation
EQ-5D-5L: baseline, and at 12, 18 and 24 weeks following randomisation
Secondary outcome [2] 307458 0
Performance status, as assessed using the self-rated Eastern Cooperative Oncology Group (ECOG) Performance Status scale and the self-rated Karnofsky Performance Status scale
Timepoint [2] 307458 0
Baseline, and at 12 and 24 weeks following randomisation
Secondary outcome [3] 307460 0
Function, as assessed using the Katz Activities of Daily Living (ADL) scale and the Older American Resources and Services (OARS) Independent Activities of Daily Living scale
Timepoint [3] 307460 0
Baseline, and at 12 and 24 weeks following randomisation
Secondary outcome [4] 307462 0
Overall survival
Timepoint [4] 307462 0
Monitored on a weekly basis until death, loss to follow-up or withdrawal of consent
Secondary outcome [5] 307463 0
Depression, as assessed using the Patient Health Questionnaire 9-item (PHQ-9) instrument
Timepoint [5] 307463 0
Baseline, and at 12 and 24 weeks following randomisation
Secondary outcome [6] 307464 0
Anxiety, as assessed using the Generalized Anxiety Disorder 7-item (GAD-7) instrument
Timepoint [6] 307464 0
Baseline, and at 12 and 24 weeks following randomisation
Secondary outcome [7] 307465 0
Nutrition, as assessed by the self-Mini Nutritional Assessment (self-MNA)
Timepoint [7] 307465 0
Baseline, and at 12 and 24 weeks following randomisation
Secondary outcome [8] 307466 0
Health utilities, as assessed using the EQ-5D-5L
Timepoint [8] 307466 0
Baseline, and at 12, 18 and 24 weeks following randomisation
Secondary outcome [9] 307467 0
Relative Dose Intensity (RDI), calculated by the ratio of delivered dose intensity of chemotherapy to standard dose for the time period, based on review of participants' medical records.
Timepoint [9] 307467 0
At 12 and 24 weeks following randomisation
Secondary outcome [10] 307468 0
Proportion of participants with dose reduction >10% from previous dose, based on review of participants' medical records.
Timepoint [10] 307468 0
At 12 and 24 weeks following randomisation
Secondary outcome [11] 307469 0
Proportion of participants with treatment delays of more than 14 days, based on review of participants' medical records.
Timepoint [11] 307469 0
At 12 and 24 weeks following randomisation
Secondary outcome [12] 307470 0
Proportion of participants with dose discontinuation, based on review of participants' medical records.
Timepoint [12] 307470 0
At 12 and 24 weeks following randomisation
Secondary outcome [13] 307492 0
Healthcare utilisation, as assessed by number of emergency department visits, number of hospital admissions, number of medical consultations and type of PBS-listed medications, based on review of the participants' medical records.
Timepoint [13] 307492 0
At 12 and 24 weeks following randomisation
Secondary outcome [14] 307496 0
Institutionalisation, as assessed by the place of residence and by the level of care, based on review of the participants' medical records.
Timepoint [14] 307496 0
Baseline, and at 12 and 24 weeks following randomisation
Secondary outcome [15] 307500 0
Healthcare cost, based on review of partcipants' medical records and Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data.

Costs will be calculated for the use of healthcare resources such as Medicare-reimbursed costs, medications (including chemotherapy), emergency department visits, hospital stays and the use of other healthcare services (including allied health, rehabilitation, aged care and palliative care).
Timepoint [15] 307500 0
At 24 weeks following randomisation

Eligibility
Key inclusion criteria
1. Aged 70 years or older
2. Pathologically confirmed solid organ cancer or diffuse large B-cell lymphoma
3. Planned for cytotoxic chemotherapy, targeted therapy or immunotherapy
4. Able to effectively understand the language of the quality of life questionnaires in one of the validated languages for the questionnaires
5. Able to give written informed consent before randomisation according to local, national and international regulations
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have received cytotoxic chemotherapy, targeted therapy or immunotherapy within 3 months prior to enrolment
2. Unable to self-complete the health-related quality of life questionnaires
3. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
4. Prior enrolment in this study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participation in the study will be completely voluntary. Potential participants will be referred by their treating clinicians to the researcher and, if interested, they will be provided with a Participant Information and Consent Form (PICF) and given sufficient time to consider whether or not to participate in the study. If they are willing to participate in the study, participants will be requested to sign the PICF and an optional Medicare Australia participant consent form. Once a participant has consented, participants will be screened for suitability according to the inclusion and exclusion criteria. If they are suitable to participate in the study, the study doctor will perform the baseline assessment prior to treatment allocation. All participants will also receive brief generic advice about nutrition and activity and will be given the Cancer Council of Victoria’s booklet on “Understanding Chemotherapy: a guide for people with cancer, their families and friends”.

Participants will be randomly assigned via a computerised system using the method of minimisation (with a 80:20 random element) to receive integrated geriatric care or standard oncology care in a 1:1 ratio. In this study, minimisation will be used to achieve balance between groups using the following characteristics: tumour type, age, gender, and ECOG performance status (physician-rated). This method will be conducted using the MinimPy software package by a researcher not involved in the care of the study participants. The allocation code will not be released until the participant has been enrolled into the study.

Allocation concealment will be ensured, as the allocation involves randomisation by computer which is operated by a researcher who is blinded to the results of all assessments and outcome measures except the variables required to allocate participants (i.e. tumour type, age, gender and ECOG performance status).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned via a computerised system using the method of minimisation (with a 80:20 random element) to receive integrated geriatric care or standard oncology care in a 1:1 ratio. In this study, minimisation will be used to achieve balance between groups using the following characteristics:
- treatment intent
- tumour type
- age
- gender
- ECOG performance status (physician-rated)

This method will be conducted using the MinimPy software package by a researcher not involved in the care of the study participants.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Cross-over not permitted
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
SAMPLE SIZE CALCULATION
The target sample for this study is based on an independent t-test at a 2-sided significance level of 0.05 to have an 80% power to detect a significant between group difference in Trial Outcome Index (TOI) from baseline to 12 weeks with an effect size of 0.5. Under these assumptions, a minimum sample size of 64 evaluable participants in each group (or a total of approximately 128 evaluable participants) who have completed the health-related quality of life (HRQoL) questionnaires at baseline and 12 weeks is required.

PRIMARY EFFICACY ANALYSIS
The primary efficacy analysis will address the primary objective of the study which is to assess the effects of integrated geriatric care on HRQoL in older adults with metastatic cancer receiving first line chemotherapy. This will involve a hierarchical set of HRQoL analyses.

The primary HRQoL analysis will to compare the longitudinal change in TOI score for significant between-group difference using linear mixed models. Sensitivity analyses will be performed using pattern-mixture models and/or joint model of longitudinal and survival data if greater than 20% of TOI data are missing and if the reasons for missing data and patterns of missing data are not missing at random.

The secondary HRQoL analyses will compare: i) the proportion of participants who experience change in TOI by at least the clinically important threshold, using Fisher’s test; and ii) time to change in TOI by at least the clinically important threshold using log-rank test.

The tertiary HRQoL analyses involve analyses using t-test or Wilcoxon test (according to normality of distribution) of all the scales of the EORTC QLQ-C30, QLQ-ELD14 and EQ-5D-5L, to complement the primary and secondary HRQoL analyses, to make full use of all HRQoL data collected and to assist in interpretation of the of the primary endpoint.

SECONDARY EFFICACY ANALYSES
Overall survival between treatment groups will be analysed using a closed hierarchical method in the following pre-specified order: (1) palliative-intent treatment subgroup; (2) overall study population; and (3) adjuvant/curative-intent treatment subgroup.

Overall survival will be estimated using the non-parametric Kaplan-Meier method. Summary statistics will be presented with appropriate confidence intervals. The non-parametric log rank test will be used to compare the two arms of the study and, if appropriate, a Cox proportional hazard model will be used to estimate the treatment effects. Additional details will be provided in the Statistical Analysis Plan (SAP).

Other secondary endpoints will be summarised according to established guidelines specific to the measurement instrument. In general, categorical variables will be tabulated and key summary statistics (mean, standard deviation, median, range, etc.) will be presented for continuous measurements. Comparisons between treatment arms will be made where appropriate and the test selected depending on the distribution. Additional details will be provided in the SAP.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
19/05/2014
Actual
18/08/2014
Date of last participant enrolment
Anticipated
Actual
5/09/2018
Date of last data collection
Anticipated
20/02/2019
Actual
Sample size
Target
128
Accrual to date
Final
154
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2234 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 2235 0
Maroondah Hospital - Ringwood East
Recruitment hospital [3] 2236 0
Yarra Ranges Health - Lilydale
Recruitment postcode(s) [1] 7913 0
3128 - Box Hill
Recruitment postcode(s) [2] 7914 0
3135 - Ringwood East
Recruitment postcode(s) [3] 7915 0
3140 - Lilydale

Funding & Sponsors
Funding source category [1] 288971 0
Hospital
Name [1] 288971 0
Eastern Health
Country [1] 288971 0
Australia
Primary sponsor type
Hospital
Name
Eastern Health
Address
5 Arnold Street, Box Hill VIC 3128
Country
Australia
Secondary sponsor category [1] 287652 0
None
Name [1] 287652 0
Address [1] 287652 0
Country [1] 287652 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290785 0
Eastern Health Human Research Ethics Committee
Ethics committee address [1] 290785 0
Ethics committee country [1] 290785 0
Australia
Date submitted for ethics approval [1] 290785 0
Approval date [1] 290785 0
14/03/2014
Ethics approval number [1] 290785 0
E20/1314
Ethics committee name [2] 293480 0
Monash University Human Research Ethics Committee
Ethics committee address [2] 293480 0
Ethics committee country [2] 293480 0
Australia
Date submitted for ethics approval [2] 293480 0
Approval date [2] 293480 0
27/05/2014
Ethics approval number [2] 293480 0
CF14/1525 - 2014000715
Ethics committee name [3] 293481 0
Department of Health Human Research Ethics Committee
Ethics committee address [3] 293481 0
Ethics committee country [3] 293481 0
Australia
Date submitted for ethics approval [3] 293481 0
Approval date [3] 293481 0
20/05/2014
Ethics approval number [3] 293481 0
9/2014

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47146 0
Prof Ian Davis
Address 47146 0
Eastern Health Clinical School
5 Arnold St, Box Hill, VIC 3128
Country 47146 0
Australia
Phone 47146 0
+61 3 9094 9546
Fax 47146 0
Email 47146 0
[email protected]
Contact person for public queries
Name 47147 0
Wee-Kheng Soo
Address 47147 0
Eastern Health Clinical School
5 Arnold St, Box Hill, VIC 3128
Country 47147 0
Australia
Phone 47147 0
+61 3 9387 1000
Fax 47147 0
Email 47147 0
[email protected]
Contact person for scientific queries
Name 47148 0
Wee-Kheng Soo
Address 47148 0
Eastern Health Clinical School
5 Arnold St, Box Hill, VIC 3128
Country 47148 0
Australia
Phone 47148 0
+61 3 9387 1000
Fax 47148 0
Email 47148 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Will need to discuss further with the study investigators but possibly will be available on request


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIntegrated Geriatric Assessment and Treatment Effectiveness (INTEGERATE) in older people with cancer starting systemic anticancer treatment in Australia: a multicentre, open-label, randomised controlled trial.2022https://dx.doi.org/10.1016/S2666-7568%2822%2900169-6
N.B. These documents automatically identified may not have been verified by the study sponsor.