Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000870954
Ethics application status
Approved
Date submitted
5/08/2011
Date registered
16/08/2011
Date last updated
14/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Anti-inflammatory and nutritional support, with simple exercises in lung cancer patients with weight loss.
Scientific title
ACCeRT: Auckland's Cancer Cachexia evaluating Resistance Training study.
EPA, Cox-2 inhibitor versus EPA, Cox-2 inhibitor, PRT plus essential amino acids intervention to assess acceptability in Non-Small-Cell Lung Cancer cachectic patients
Secondary ID [1] 262787 0
Nil
Universal Trial Number (UTN)
1111 – 1123 - 4962
Trial acronym
ACCeRT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer cachexia 270494 0
Condition category
Condition code
Cancer 270653 270653 0 0
Lung - Non small cell
Diet and Nutrition 270730 270730 0 0
Other diet and nutrition disorders
Inflammatory and Immune System 270731 270731 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm A ‘International best supportive care’ is defined as 2g /day of EPA oral and 300mg / day of COX-2 inhibitor (Celebrex) oral for 20 weeks. Arm B ‘Treatment group’ is defined as 2g / day of EPA oral, 300mg / day of COX-2 inhibitor (Celebrex) oral, Progressive Resistance Training (2 episodes per week, involving 5-10 minute warmup, 10-15 minutes resistance training followed by 5 minute cool-down, approximately 30 minutes increasing in time to 1 hour per session, commencing on a one-to-one basis and moving onto a group sessions if required by participant, under supervision of a trained exercise therapist) plus 20g essential amino acids high in leucine over 3 days commencing 1 hour post exercise, oral, for 20 weeks.
Intervention code [1] 269130 0
Treatment: Other
Intervention code [2] 269192 0
Rehabilitation
Intervention code [3] 269193 0
Lifestyle
Comparator / control treatment
Arm A
‘International best supportive care’ is defined as EPA and COX-2 inhibitor
Control group
Active

Outcomes
Primary outcome [1] 269373 0
Primary Outcome 1: The acceptability of the treatment regimen will be assessed by asking patients to complete a questionnaire asking if they found the regimen acceptable and if they wish to continue with the treatment.
Timepoint [1] 269373 0
Timepoint: at visit 5 / week 12 and End of Study visit
Secondary outcome [1] 279490 0
Secondary measured outcome 1: Lean body mass assessed by bioelectrical impedance analysis (Tanita BC-418 Segmental Body Composition Analyzer, Tanita)
Timepoint [1] 279490 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [2] 279491 0
Secondary outcome 2
MRI thigh skeletal muscle values as assessed (treatment allocation is blinded) by University MRI department
Timepoint [2] 279491 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [3] 279492 0
Secondary measured outcome 3: QoL and fatigue assessed by the following questionnaires MFSI-SF, FAACT, WHOQOL-BREF
Timepoint [3] 279492 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [4] 279493 0
Secondary Outcome 4:
Serum levels of proinflammatory classic cachexia cytokines (IL-1, IL-6 and TNF-alpha) measured by Bio-Plex Pro assay, Bio-Rad)
Timepoint [4] 279493 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [5] 279494 0
Secondary outcome 5: Hand grip strength assessed by hand grip dynamometry of the dominant hand, the average of three attempts with 1 minute rest between attempts
Timepoint [5] 279494 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [6] 279495 0
Secondary outcome 6: Leg strength assessed by a customised leg extension rig (chair) with a cell load of the right leg, the average of three attempts with a 1 minute rest between attempts
Timepoint [6] 279495 0
Screening visit or week 1 and week 20 after intervention commencement
Secondary outcome [7] 294362 0
Secondary safety outcome 1: Serious Adverse Events (SAEs) and Adverse Events (AEs) e.g cardiac changes on ECG. All symptoms assessed using the NCI CTC
Timepoint [7] 294362 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [8] 294363 0
Secondary safety outcome 2: Glasgow Prognotic Score (GPS)
Timepoint [8] 294363 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [9] 294364 0
Secondary safety outcome 3: Karnofsky Score (KS)
Timepoint [9] 294364 0
Timepoint: Screening visit, week 1, 3, 6, 9, 12, 16 and 20 after intervention commencement
Secondary outcome [10] 294365 0
Secondary safety outcome 4: Progression-Free Survivial (PFS) will be assessed from the date of consent until documented radiology proven (CT) progression
Timepoint [10] 294365 0
End of study (1-2 weeks post study)
Secondary outcome [11] 294366 0
Secondary safety outcome 5: Overall compliance will be assessed by returned study medication and the number of PRT sessions attended
Timepoint [11] 294366 0
End of study (1-2 weeks post study)
Secondary outcome [12] 294367 0
Secondary safety outcome 7: RECIST data (if avalible)
Timepoint [12] 294367 0
End of study (1-2 weeks post study)

Eligibility
Key inclusion criteria
Patients who have diagnosed NSCLC and have received at least a first-line anti-cancer treatment e.g. surgery, chemotherapy, radiotherapy or a targeted therapy (i.e. gefitinib, erlotinib and crizotinib) and fulfil the following cachexia definition Q1 Has lost 5% of oedema-free body weight in the previous 12 months or less Q2 Mild less than or equal to 5%, Moderate greater than 10%, Severe greater than 15% Q3 If no documented weight loss, Is BMI of less than 20.0 kg/m2 Q4 At least 3 out of the following 5 1. Decreased muscle strength 2. Experiencing fatigue either measured by a VO2 max score or patient confirmed reduced physical activity 3. Anorexia 4. Low fat-free mass index (low muscle mass) 5. Abnormal biochemistry, CRP greater than 5.0mg/L IL-6 greater than 4.0pg/ml anaemia Hb less than 12.0g/dL hypoalbuminemia less than 3.2g/dL Inclusion criteria: 1. Patients greater than or equal to 18 years old 2. Histologically confirmed non-small cell carcinoma of the lung. (Histological or cytological specimens must be collected via surgical biopsy, brushing, washing or core needle aspiration of a defined lesion. Sputum cytology is not acceptable) 3. Patients should be aware of the diagnosis of cancer 4. Patients able to give written informed consent obtained according to local guidelines 5. Fulfils above ‘cachectic definition’ 6. Karnofsky Scoreequal to 60 or ECOG Performance Status 0,1, 2 or 3 7. Recently completed first-line platinum-based chemotherapy 8. Lab values within the range, as defined below, within 2 weeks of randomisation: 1. Absolute neutrophils count (ANC) greater than 2.0 x 109/L 2. Platelets greater than or equal to 100 x 109/L 3. Haemoglobin greater than or equal to 100 g/dL 4. Serum creatinine less than or equal to 1.5 x ULN (= 120 micro mol/L) 5. Serum bilirubin less than or equal to 1.5 x ULN (= 25 micro mol/L) 6. Aspartate transaminase (AST) and alanine transaminase (ALT)less than or equal to 2.5 x ULN (less than or equal to 5 x ULN if liver metastases) 7. Electrolyte values (potassium, calcium, magnesium) within greater than 1 x LLN and less than 1 x ULN 8. Females of child-bearing potential must have negative serum pregnancy test (confirmation of negative urine pregnancy test within 72 hours prior to initial dosing) 9. Life expectancy greater or equal to 20 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
1. Patients who are, in the opinion of a doctor or nurse in the department, unlikely to be suitable to participate by virtue of mental incapacity, severe current psychological or psychiatric disorder
2. Patients with an estimated prognosis of less than one month
3. Concurrent use of other investigational agents and patients who have received investigational agents in the last 4 weeks prior to randomisation
4. Concurrent use of other appetite stimulants e.g. MPA or MA and 4mg OD dexamethasone or 30mg OD prednisolone
5. Patients with systolic BP > 160 mm HG and/or diastolic > 90 mm HG
6. Pleural effusion that causes a CTC grade 2 dyspnoea
7. Radiotherapy in the last 2 weeks prior to randomisation. Patients must have recovered from all radiotherapy-related toxicities
8. Patients with a history of another primary malignancy within last 5 years with the exception of non-melanoma skin cancer or cervical cancer in situ
9. Patients having CNS metastases (Patients having any clinical signs of CNS metastases must have a CT or MRI of the brain performed to rule out CNS metastases in order to be eligible for study participation. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed)
10. Patients with recent haemoptysis associated with NSCLC (> 1 teaspoon in a single episode within 4 weeks)
11. Patients with an abnormal Baseline 12-lead ECG
12. Concurrent severe and/or uncontrolled medical disease (i.e. uncontrolled diabetes, chronic renal failure, chronic liver disease
Patient unwilling or unable to comply with the study protocol

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)
After patients complete the screening procedures at the Screening Visit and the principal investigator has confirmed that all inclusion/exclusion criteria have been met, all eligible patients will be randomly assigned to a treatment arm. Enclosed treatment assignments will be serially numbered in opaque, sealed envelopes and opened sequentially after the participant’s name and other details have been written on the appropriate envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Enclosed treatment assignments will be serially numbered in opaque, sealed envelopes and opened sequentially after the participant’s name and other details have been written on the appropriate envelope. Simple randomisation by using a randomisation table created by coputer software (i.e computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
1:2 randomisation
Arm A 1: Arm B 2.
Phase
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2011
Actual
5/06/2012
Date of last participant enrolment
Anticipated
Actual
19/05/2015
Date of last data collection
Anticipated
Actual
13/10/2015
Sample size
Target
21
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 3770 0
New Zealand
State/province [1] 3770 0
Auckland

Funding & Sponsors
Funding source category [1] 269607 0
University
Name [1] 269607 0
University of Auckland
Country [1] 269607 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
38-42 Wharf Road
West Ryde
NSW 2114
Country
Australia
Secondary sponsor category [1] 266639 0
Commercial sector/Industry
Name [1] 266639 0
Health World Limited
Address [1] 266639 0
741 Nudgee Road
Northgate
QLD 4013
Country [1] 266639 0
Australia
Secondary sponsor category [2] 266640 0
Commercial sector/Industry
Name [2] 266640 0
Musashi
Address [2] 266640 0
Nestle Performance Nutrition
16 Howleys Road
Notting Hill
VIC 3168
Country [2] 266640 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269556 0
Northern Y Ethics Committee
Ethics committee address [1] 269556 0
Ethics committee country [1] 269556 0
New Zealand
Date submitted for ethics approval [1] 269556 0
11/06/2011
Approval date [1] 269556 0
02/09/2011
Ethics approval number [1] 269556 0

Summary
Brief summary
Cancer cachexia is a syndrome of progressive weight loss, anorexia, and persistent reduction of body cell mass in response to a malignant tumour. In cancer cachexia there is the extensive loss of adipose tissue and equal amounts of skeletal muscle mass. The incidence of cachexia is type of tumour and site dependent. Small-Cell and NSCLC patients experience a high incidence of cachexia, 57% and 61% respectively. It is associated with a deterioration of functional status and quality of life and is also associated with poor survival. Muscle wasting is the main cause of impaired function, leading to respiratory complications and fatigue.There is a need to support cachectic lung cancer patients after their chemotherapeutic regimens, especially with the added knowledge that chemotherapy treatment will add to their overall weight loss and cachectic state. The optimal treatment for cancer cachexia is the complete removal of the tumour; unfortunately with many advanced solid tumours this is unachievable, especially in the case of NSCLC patients. The next best options are to increase nutritional intake to counteract the weight loss, address the anorexia, inflammation, and the metabolic alterations i.e. loss of body fat and the skeletal muscle wasting. This study aims to identify a novel treatment
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32982 0
Prof Bruce Arroll
Address 32982 0
University of Auckland School of Population Health Department of General Practice and Primary Health Care Tamaki Campus Cnr Morrin Road and Merton Road Glenn Innes Auckland 1072
Country 32982 0
New Zealand
Phone 32982 0
+ 64 9 373 7599 ext 86746
Fax 32982 0
+ 64 9 373 7624
Email 32982 0
[email protected]
Contact person for public queries
Name 16229 0
Dr Rita Sasidharan
Address 16229 0
Department of Oncology
Auckland City Hospital
2 Park Road
Grafton
Auckland
1023
Country 16229 0
New Zealand
Phone 16229 0
+ 64 9 307 4949 ext 6242 (Clinical trials)
Fax 16229 0
+ 64 9 359 9981 (Clinical trials)
Email 16229 0
[email protected]
Contact person for scientific queries
Name 7157 0
Dr Rita Sasidharan
Address 7157 0
Department of Oncology
Auckland City Hospital
2 Park Road
Grafton
Auckland
1023
Country 7157 0
New Zealand
Phone 7157 0
+ 64 9 307 4949 ext 6242 (Clinical trials)
Fax 7157 0
+ 64 9 359 9981 (Clinical trials)
Email 7157 0
[email protected]

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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